Gene Summary

Gene:CCK; cholecystokinin
Summary:This gene encodes a member of the gastrin/cholecystokinin family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the peptide hormones cholecystokinin-8, -12, -33, and others. The encoded peptides have been shown to regulate gastric acid secretion and food intake. A sulfated form of cholecystokinin-8 may modulate neuronal activity in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (11)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Lung CancerCCK and Lung Cancer View Publications112
Liver CancerCCK and Liver Cancer View Publications97
Breast CancerCCK and Breast Cancer View Publications93
Pancreatic CancerCCK and Pancreatic Cancer View Publications77
Ovarian CancerCCK and Ovarian Cancer View Publications55
OsteosarcomaCCK and Osteosarcoma View Publications54
Prostate CancerCCK and Prostate Cancer View Publications39
Cervical CancerCCK and Cervical Cancer View Publications34
Colorectal CancerCCK and Colonic Neoplasms View Publications28
Thyroid CancerCCK and Thyroid Cancer View Publications24
Ewing's SarcomaCCK Expression in Ewing's Sarcoma
In a study of diverse tumour cell lines Friedman (1992) reported that only a subset of tumors were found to expresses the cholecystokinin gene, in particular; 8/8 neuroepitheliomas, 8/8 Ewing sarcoma amd 2/6 rhabdomyosarcoma. In a study of paediatric primary tumours Schaer (1999) found that CCK cRNA expression was predominatly resrticted to 9/11 Ewing sarcomas and 5/10 leiomyosarcomas.
View Publications7

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: CCK (cancer-related)

Huang D, Wei Y, Zhu J, Wang F
Long non-coding RNA SNHG1 functions as a competitive endogenous RNA to regulate PDCD4 expression by sponging miR-195-5p in hepatocellular carcinoma.
Gene. 2019; 714:143994 [PubMed] Related Publications
Long non-coding RNA (lncRNA) potentially regulates tumorigenesis. LncRNA small nucleolar RNA host gene 1 (SNHG1) expression remains high in hepatocellular carcinoma cells; however, its biological mechanism in hepatocellular carcinoma remains unknown. In this study, SNHG1 expression in hepatocellular carcinoma cells was detected by qRT-PCR. Proliferative and migratory potentials of hepatocellular carcinoma cells were determined by CCK-8 and Transwell assay, respectively. Then, the nude mice model of xenograft was employed to verify the effect of SNHG1 on tumor formation in vivo. We identified the potential target of SNHG1 through bioinformatics and dual-luciferase reporter gene. Furthermore, Western blot and RIP assay was used for clarifying their interaction and functions in regulating the development of hepatocellular carcinoma. Our results indicated a high expression of SNHG1 in hepatocellular carcinoma cells. Downregulation of SNHG1 inhibited proliferative and migratory potentials of hepatocellular carcinoma cells in vitro and in vivo. Moreover, the expression of programmed cell death 4 (PDCD4) was positively regulated by SNHG1 through competing with miR-195-5p. These results indicated that SNHG1 participated in the development of hepatocellular carcinoma as a ceRNA to competitively bind to miR-195-5p and thus mediate PDCD4 expression.

Liu M, Gong C, Xu R, et al.
MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2.
Cell Mol Biol Lett. 2019; 24:47 [PubMed] Free Access to Full Article Related Publications
Background: Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells.
Methods: The study used both PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. The expression of miR-5195-3p was determined using quantitative real-time PCR. Cell viability, cell cycle distribution and apoptosis were analyzed using CCK-8 and flow cytometry assays. The target genes of miR-5195-3p were predicted with bioinformatics analysis and confirmed using the luciferase reporter assay.
Results: MiR-5195-3p expression was lower in PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. Upregulation of miR-5195-3p enhanced the sensitivity of PTX-resistant TNBC cells to PTX treatment. EIF4A2 was confirmed as a potential target of miR-5195-3p. EIF4A2 knockdown imitated the effects of miR-5195-3p on chemosensitivity, while restoration of EIF4A2 rescued them.
Conclusion: These data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.

Guo Q, Wang L, Zhu L, et al.
The clinical significance and biological function of lncRNA SOCAR in serous ovarian carcinoma.
Gene. 2019; 713:143969 [PubMed] Related Publications
BACKGROUND: Ovarian cancer (OvCa) is one of the most lethal gynecologic malignancies worldwide. Pelvic and abdominal metastasis is a leading cause for the poor prognosis of OvCa patients. The relationship between long non-coding RNAs (lncRNAs) and OvCa remains unclear. Identifying key lncRNAs related with OvCa metastasis is crucial for research on the mechanism of OvCa metastasis. This study was designed to investigate the role of a novel lncRNA, which we named SOCAR, in serous OvCa.
METHODS: LncRNA microarray and Real-time PCR were used to examine SOCAR expression in high grade serous ovarian cancer (HGSOC) and normal ovary tissues. The proliferation, migration and invasion of OvCa cell lines SKOV-3 and OVCAR-3 were analyzed by CCK-8, Transwell and Scratch wound healing assays. Western blotting was used to detect the expression of Wnt/β-catenin pathway-related proteins.
RESULTS: A novel serous OvCa-related lncRNA, SOCAR, was identified via microarray. SOCAR was overexpressed in primary HGSOC tumors compared with normal ovary tissues, and the expression of SOCAR correlated with progression in HGSOC patients. SOCAR also had higher expression in metastatic HGSOC tissues compared with primary cancer tissues. Moreover, upregulation of SOCAR promoted proliferation, migration and invasion in OvCa cells. Expression of Wnt1, β-catenin and MMP-9 were all increased by SOCAR overexpression.
CONCLUSION: SOCAR is related with HGSOC oncogenesis and progression. It may promote proliferation, migration and invasion in OvCa cells partially by upregulating MMP-9 through the Wnt/β-catenin pathway.

Chai L, Yang G
MiR-216a-5p targets TCTN1 to inhibit cell proliferation and induce apoptosis in esophageal squamous cell carcinoma.
Cell Mol Biol Lett. 2019; 24:46 [PubMed] Free Access to Full Article Related Publications
Background: MiR-216a-5p has been reported to be associated with several tumors, including prostate cancer and melanoma. However, its expression level and potential role in esophageal squamous cell carcinoma (ESCC) remain uncertain.
Results: Here, we found that miR-216a-5p expression was significantly down-regulated in clinical ESCC tissues and cells. Functional assays were performed to evaluate the biological effects of miR-216a-5p on cell proliferation and cell apoptosis by CCK-8 assay and flow cytometry in ESCC cell lines, EC9706 and TE-9. The results showed that miR-216a-5p overexpression repressed cell proliferation and induced cell apoptosis. Through bioinformatics prediction and luciferase reporter assay, we revealed that miR-216a-5p could directly target tectonic family member 1 (TCTN1). Moreover, TCTN1 was obviously suppressed by miR-216a-5p overexpression. In addition, TCTN1 expression was significantly increased and inversely correlated with the levels of miR-216a-5p in ESCC tissues. More importantly, down-regulation of TCTN1 imitated, while restoration of TCTN reversed the effects of miR-216a-5p on cell proliferation and apoptosis. At the molecular level, we further found that TCTN1 overexpression reversed the effects of miR-216a-5p transfection on the expression of PCNA, Bcl-2 and Bad.
Conclusions: Our results demonstrate that miR-216a-5p might serve as a tumor suppressor in ESCC cells through negatively regulating TCTN1 expression, indicating the possibility that miR-216a-5p and TCTN1 might be attractive targets for ESCC therapeutic intervention.

Zhang Y, Zhang Y, Xu H
LIMCH1 suppress the growth of lung cancer by interacting with HUWE1 to sustain p53 stability.
Gene. 2019; 712:143963 [PubMed] Related Publications
BACKGROUND: The aim of this study was to identify the expression of LIM and calponin-homology domains 1 (LIMCH1) in lung cancer and normal tissues, to determine the interaction between LIMCH1 and HUWE1 in regulating p53 stability.
METHODS: The expression of LIMCH1 was detected by the Oncomine and Cancer Genome Atlas databases. Expression of LIMCH1 mRNA was identified using qRT-PCR. In transfected human lung cancer cells, co-immunoprecipitation experiments were performed. The mechanism that HUWE1 sustained lung cancer malignancy was verified by western blotting. The proliferation of tranfected cells was assessed by CCK-8 assay and colony formation.
RESULTS: Bioinformatic data and e TCGA database suggested LIMCH1 mRNA levels in tumor tissues were down-regulated compared to tumor adjacent tissues. We found low expression of LIMCH1 mRNA in tumor sites and tumor cell line. Exogenous expression of LIMCH1 interacts with HUWE1 promotes expression of p53. Use of siRNA or shRNA against LIMCH1 resulted in decreased p53 protein levels. LIMCH1 deletion lead to enhance of p53 ubiquitination and protein expression of p53 and substrate p21, puma. Growth curve showed that LIMCH1 deletion significantly promoted the proliferation of A549 cells.
CONCLUSIONS: LIMCH1 was a negative regulator and indicated a new molecular mechanism for the pathogenesis of lung cancer via modulating HUWE1 and p53.

Tao L, Wu YQ, Zhang SP
MiR-21-5p enhances the progression and paclitaxel resistance in drug-resistant breast cancer cell lines by targeting PDCD4.
Neoplasma. 2019; 2019 [PubMed] Related Publications
MiR-21-5p has been identified as an oncogene to enhance human tumor progression. Here, we explored the mechanism by which miR-21-5p regulated the progression and paclitaxel (PTX) resistance in drug-resistant breast cancer (BC) cell lines. qRT-PCR assays were used to assess the expression levels of miR-21-5p and PDCD4 mRNA, and western blotting was used to detect PDCD4 protein level in PTX-resistant BC cell lines. Dual-luciferase reporter assay was used to observe the interaction between miR-21-5p and PDCD4 in PTX-resistant BC cell lines. Cell proliferation ability and IC50 values of PTX were measured by CCK-8 assay, cell cycle progression and apoptosis were determined with flow cytometry analysis, and cell migration and invasion capacities were analyzed using Transwell assay. Xenograft mice assay was used to validate the important role of miR-21-5p as a regulator on PTX-resistance BC cells growth in vivo. Then, we found that miR-21-5p was upregulated and PDCD4 was downregulated in BC tissues and PTX-resistant BC cell lines. MiR-21-5p silencing or PDCD4 overexpression ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines. Moreover, PDCD4 was demonstrated to be a direct target of miR-21-5p. MiR-21-5p exerted its regulatory effect by PDCD4 in PTX-resistant BC cell lines. Additionally, miR-21-5p silencing inhibited tumor growth in vivo. Therefore, our study demonstrated that miR-21-5p silencing ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines at least partly by targeting PDCD4, providing miR-21-5p as an effective therapeutic target for PTX-resistant BC treatment.

Mai L, Luo M, Wu JJ, et al.
The combination therapy of HIF1α inhibitor LW6 and cisplatin plays an effective role on anti-tumor function in A549 cells.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Hypoxia-inducible factor 1α (HIF1α) has been demonstrated to be involved in the resistance of various human cancer cells to chemotherapies. However, the correlation between HIF1α and the sensitivity of human non-small cell lung cancer (NSCLC) cells to cisplatin has not been illuminated. The aim of the present study was to investigate the effects of HIF1α on drug resistance in NSCLC cells. A549 cells were incubated in 21% or 0.5% O2 followed by the assessment of the level of HIF1α with qRT-PCR and western blot and ROS level by DCFH-DA assays. Effects of hypoxia or HIF1α inhibitor LW6 on the proliferation and apoptosis of A549 cells were evaluated via CCK-8 and flow cytometry assays. IC50 of A549 cells to cisplatin was determined by MTT assay. The mitochondrial membrane potential (MMP) was measured via JC-1 staining. Moreover, the expression of apoptosis related protein (Bcl-2, Bax) and drug resistance related proteins (MDR1, MRP1) were measured by western blotting. Exposure of A549 cells to 1% O2 significantly up-regulated HIF1α expression, maintained cell viability to cisplatin but decreased the ROS level, which promoted chemoresistance to cisplatin. LW6-treated A549 cells showed an increase in ROS level that blocked the hypoxia induced resistance to cisplatin and in addition, decreased expression of MDR1 and MRP1 in cisplatin-treated cells. This study revealed that hypoxia-improved cisplatin chemoresistance of NSCLC cells by regulated MDR1 and MRP1 expression via HIF1α/ROS pathway is reversed by LW6, suggesting that LW6 may act as effective sensitizer in chemotherapy for NSCLC.

Lu G, Zhang Y
MicroRNA-340-5p suppresses non-small cell lung cancer cell growth and metastasis by targeting ZNF503.
Cell Mol Biol Lett. 2019; 24:34 [PubMed] Free Access to Full Article Related Publications
Background: MicroRNAs (miRNAs) have been reported to play crucial roles in cancer cell processes, including proliferation, metastasis and cell cycle progression. We aimed to identify miRNAs that could act as suppressors of cell growth and invasion in non-small cell lung cancer (NSCLC).
Methods: Fifteen paired NSCLC tissue samples and pericarcinomatous normal tissues were collected and preserved in liquid nitrogen. The expression levels of miR-340-5p and ZNF503 mRNA were detected using a qPCR assay. The transfection of plasmids was conducted using Lipofectamine 3000 according to the manufacturer's protocol. Cell proliferation was determined using a CCK-8 assay. The protein levels of endothelial-mesenchymal transition markers were measured using a western blot assay. Cell invasive ability was evaluated using a transwell assay. TargetScan was used to predict targets of miR-340. A dual luciferase reporter assay was performed to confirm a potential direct interaction between miR-340-5p and ZNF503.
Results: The expression level of miR-340-5p was frequently found to be lower in NSCLC tissues than in matched pericarcinomatous normal tissues. Overexpression of miR-340-5p significantly inhibited the proliferation and invasion NCI-H1650 (a NSCLC cell line), while inhibition of miR-340-5p stimulated cell growth. Using TargetScan, we predicted that ZNF503 could be a target of miR-340-5p. Further mechanistic studies demonstrated that the forced expression of ZNF503 could partially abrogate the miR-340-5p-mediated decrease in NCI-H1650 cell viability and invasion, suggesting that miR-340-5p suppressed cell growth and invasion in a ZNF503-dependent manner.
Conclusion: Our findings indicate that miR-340-5p inhibits NCI-H1650 cell proliferation and invasion by directly targeting ZNF503 and that miR-340-5p can serve as a potential therapeutic target for treating NSCLC.

Wang X, Lyu J, Ji A, et al.
Jarid2 enhances the progression of bladder cancer through regulating PTEN/AKT signaling.
Life Sci. 2019; 230:162-168 [PubMed] Related Publications
AIMS: Jumonji AT-rich interactive domain 2 (Jarid2) is an interacting component of PRC2 which catalyzes methylation of H3K27 (H3K27me3) and causes the downregulation of PTEN. In the present study, we aimed to explore whether Jarid2 could interact with H3K27me3 to regulate PTEN expression in bladder cancer.
MAIN METHODS: Jarid2 expression in bladder cancer tissues and cells were determined by western blotting and RT-PCR. CCK-8, flow cytometry, transwell chamber and in vivo xenograft assays were performed to assess cell growth, apoptosis, migration and tumorigenesis, respectively. Chromatin immunoprecipitation (ChIP) assay was used to assess the methylation of PTEN.
KEY FINDINGS: Jarid2 expression was increased in bladder cancer tissues and cells. Downregulation of Jarid2 with shRNA transfection obviously inhibited the proliferation, migration and tumorigenesis of bladder cancer T24 and HT-1376 cells and induced cell apoptosis. Jarid2 downregulation decreased the expression of p-AKT and increased PTEN expression. Besides, Jarid2 down-regulation repressed the epithelial-mesenchymal transition (EMT), whereas knockdown of PTEN impaired this effect. Moreover, upregulation of Jarid2 increased the combination of PTEN promoter and H3K27me3, and 5-aza-CdR rescued it. Meanwhile, 5-aza-CdR administration abolished Jarid2 roles in the promotion of EMT process and AKT activation, as well as the reduction of PTEN expression.
SIGNIFICANCE: Overall, the present study elaborated that Jarid2 facilitated the progression of bladder cancer through H3K27me3-mediated PTEN downregulation and AKT activation, which might provide a new mechanism for Jarid2 in promoting bladder cancer progression.

Wang X, Wang Z, Zhang Y, et al.
Golgi phosphoprotein 3 sensitizes the tumour suppression effect of gefitinib on gliomas.
Cell Prolif. 2019; 52(4):e12636 [PubMed] Related Publications
OBJECTIVES: We previously reported that Golgi phosphoprotein 3 (GOLPH3) promotes glioma progression by inhibiting EGFR endocytosis and degradation, leading to EGFR accumulation and PI3K-AKT pathway over-activation. In the current study, we examine whether GOLPH3 affects the response of glioma cells to gefitinib, an EGFR selective inhibitor.
MATERIALS AND METHODS: The expression of GOLPH3 and EGFR in glioma cells was detected by immunofluorescence and immunoblotting. The cell viability or growth in vitro was determined by CCK-8, EdU incorporation and clonogenic assays. The primary glioma cells were cultured by trypsin and mechanical digestion. The transwell invasion assay was used to examine the primary glioma cell motility. Intracranial glioma model in nude mice were established to explore the sensitivity of gefitinib to GOLPH3 high cancer cells in vivo.
RESULTS: Both the immortalized and primary glioma cells with GOLPH3 over-expression hold higher EGFR protein levels on the cell membrane and exhibited higher sensitivity to gefitinib. In addition, primary glioma cells with higher GOLPH3 level exhibited stronger proliferation behaviour. Importantly, GOLPH3 enhanced the anti-tumour effect of gefitinib in vivo. Consistently, after gefitinib treatment, tumours derived from GOLPH3 over-expression cells exhibited lower Ki67-positive and higher cleaved caspase-3-positive cells than control tumours.
CONCLUSIONS: Our results demonstrate that GOLPH3 increases the sensitivity of glioma cells to gefitinib. Our study provides foundation for further exploring whether GOLPH3 high gliomas will be more sensitive to anti-EGFR therapy in clinic and give ideas for developing new possible treatments for individual glioma patients.

Li X, Ding D, Yao J, et al.
Chromatin remodeling factor BAZ1A regulates cellular senescence in both cancer and normal cells.
Life Sci. 2019; 229:225-232 [PubMed] Related Publications
AIMS: Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. We aim to investigate the functional role of BAZ1A in regulating senescence in cancer and normal cells.
MATERIALS AND METHODS: Knockdown of BAZ1A was performed via lentivirus mediated short hairpin RNA (shRNA) in various cancer cell lines (A549 and U2OS) and normal cells (HUVEC, NIH3T3 and MEF). A series of senescence-associated phenotypes were quantified by CCK-8 assay, SA-β-Gal staining and EdU incorporation assay, etc. KEY FINDINGS: Knockdown (KD) of BAZ1A induced series of senescence-associated phenotypes in both cancer and normal cells. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes in human cancer cells (A549 and U2OS).
SIGNIFICANCE: Our results revealed chromatin remodeling modulator BAZ1A acting as a novel regulator of cellular senescence in both normal and cancer cells, indicating a new target for potential cancer treatment.

Li D, Hao S, Zhang J
Long non-coding RNA UCA1 exerts growth modulation by miR-15a in human thyroid cancer TPC-1 cells.
Artif Cells Nanomed Biotechnol. 2019; 47(1):1815-1822 [PubMed] Related Publications
Thyroid cancer is widely diagnosed as malignancy in endocrine system. This study attempted to validate UCA1 possessed modulatory function on cell proliferation and epithelial mesenchymal transition (EMT) in human thyroid cancer cell line TPC-1. Ectopic expression of UCA1 was induced in TPC-1 cells by transfection. CCK-8 assays were employed to value cell viability. Cell apoptosis analysis was conducted through flow cytometry. We found that overexpressed UCA1 strongly promoted cell proliferation. However, the knockdown of UCA1 suppressed cell proliferation and induced obvious cell apoptosis. Besides, cell EMT was promoted by overexpressed UCA1 and was inhibited by the knockdown of UCA1. Further study revealed that miR-15a level in TPC-1 cells was suppressed by overexpressed UCA1. Simultaneous overexpression of UCA1 and miR-15a partly alleviated UCA1-induced growth, identifying that miR-15a was a possible target of UCA1. At last, the Hippo and JNK signal pathways were activated by overexpressed UCA1 but were then weakened by the adding of miR-15a. In conclusion, our study revealed UCA1/miR-15a axis implicated in thyroid cancer cells EMT, exposing a novel mechanism of thyroid cancer progression.

Zhang C, Wang W, Lin J, et al.
lncRNA CCAT1 promotes bladder cancer cell proliferation, migration and invasion.
Int Braz J Urol. 2019 May-Jun; 45(3):549-559 [PubMed] Related Publications
OBJECTIVE: To study the expression patterns of long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) and the changes in cell proliferation, apoptosis, migration and invasion induced by silencing CCAT1 in bladder cancer cells.
MATERIALS AND METHODS: The expression levels of CCAT1 were determined using realtime quantitative polymerase chain reaction in cancerous tissues and paired normal tissues from 34 patients with bladder cancer. The relationship between clinical characteristics and CCAT1 expression was analyzed. And then we conducted cell experiments. Bladder urothelial carcinoma cell lines T24 and 5637 cells were transfected with CCAT1 small interfering RNA (siRNA) or scramble siRNA. Cell proliferation and apoptosis changes were determined using a Cell Counting Kit-8 (CCK-8) assay and a fl ow cytometry assay. Migration and invasion changes were measured using a wound healing assay and a trans-well assay. microRNAs (miRNAs) were predicted by Starbase 2.0, and their differential expression levels were studied.
RESULTS: CCAT1 was signifi cantly upregulated in bladder cancer (P < 0.05). CCAT1 upregulation was positively related to tumor stage (P = 0.004), tumor grade (P = 0.001) and tumor size (P = 0.042). Cell proliferation, migration and invasion were promoted by abnormally expressed CCAT1. miRNAs miR-181b-5p, miR-152-3p, miR-24-3p, miR-148a-3p and miR-490-3p were potentially related to the aforementioned functions of CCAT1.
CONCLUSION: CCAT1 plays an oncogenic role in urothelial carcinoma of the bladder. In addition, CCAT1 may be a potential therapeutic target in this cancer.

Ding L, Zhang H
Circ-ATP8A2 promotes cell proliferation and invasion as a ceRNA to target EGFR by sponging miR-433 in cervical cancer.
Gene. 2019; 705:103-108 [PubMed] Related Publications
Cervical cancer (CC), a common gynecological carcinoma, is a serious threat to women's health. The dysregulation of circular RNAs (circRNAs) is associated with the pathogenesis of cervical cancer. Therefore, we explored the role of circ-ATP8A2 in CC cell development and progression. Circ-ATP8A2 profiles in CC specimens and cells were detected using real-time PCR. In addition, cell counting kit-8 (CCK-8), acridine orange/ethidium bromide (AO/EB), flow cytometric, and Transwell experiments were carried out on HeLa and SW756 cells to determine cell proliferation, apoptosis, migration and invasion. Furthermore, the mechanism of circ-ATP8A2 was explored by dual-luciferase reporter system. Circ-ATP8A2 was significantly enhanced in CC specimens and cells. Knockdown of circ-ATP8A2 inhibited cell proliferation, migratory and invasive capacities and increased apoptotic cells. Ectopically expressed circ-ATP8A2 induced the opposite effects. For the mechanism exploration, circ-ATP8A2 sponges miR-433 to release its suppression on epidermal growth factor receptor (EGFR) expression at post-transcriptional level. What's more, circ-ATP8A2 could promote cell progression by miR-433/EGFR axis in CC cells. Collectively, this work might offer a potential treatment target for CC. ABBREVIATIONS.

Wu AY, Gu LY, Cang W, et al.
Fn14 overcomes cisplatin resistance of high-grade serous ovarian cancer by promoting Mdm2-mediated p53-R248Q ubiquitination and degradation.
J Exp Clin Cancer Res. 2019; 38(1):176 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the most lethal of all gynecological malignancies. Patients often suffer from chemoresistance. Several studies have reported that Fn14 could regulate migration, invasion, and angiogenesis in cancer cells. However, its functional role in chemoresistance of HGSOC is still unknown.
METHODS: The expression of Fn14 in tissue specimens was detected by IHC. CCK-8 assay was performed to determine changes in cell viability. Apoptosis was measured by flow cytometry. The potential molecular mechanism of Fn14-regulated cisplatin resistance in HGSOC was investigated using qRT-PCR, western blotting, and Co-IP assays. The role of Fn14 in HGSOC was also investigated in a xenograft mouse model.
RESULTS: In this study, we found that Fn14 was significantly downregulated in patients with cisplatin resistance. Patients with low Fn14 expression were associated with shorter progression-free survival and overall survival. Overexpression of Fn14 suppressed cisplatin resistance in OVCAR-3 cells, whereas knockdown of Fn14 did not affect cisplatin resistance in SKOV-3 cells. Interestingly, Fn14 could exert anti-chemoresistance effect only in OVCAR-3 cells harboring a p53-R248Q mutation, but not in SKOV-3 cells with a p53-null mutation. We isolated and identified primary cells from two patients with the p53-R248Q mutation from HGSOC patients and the anti-chemoresistance effect of Fn14 was observed in both primary cells. Mechanistic studies demonstrated that overexpression of Fn14 could reduce the formation of a Mdm2-p53-R248Q-Hsp90 complex by downregulating Hsp90 expression, indicating that degradation of p53-R248Q was accelerated via Mdm2-mediated ubiquitin-proteasomal pathway.
CONCLUSION: Our findings demonstrate for the first time that Fn14 overcomes cisplatin resistance through modulation of the degradation of p53-R248Q and restoration of Fn14 expression might be a novel strategy for the treatment of HGSOC.

Ma Q, Gao Y, Xu P, et al.
Atorvastatin Inhibits Breast Cancer Cells by Downregulating PTEN/AKT Pathway via Promoting Ras Homolog Family Member B (RhoB).
Biomed Res Int. 2019; 2019:3235021 [PubMed] Free Access to Full Article Related Publications
Background: Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer.
Methods: The effects of ATO on breast tumor cells
Results: ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66-0.83],
Conclusions: The exact mechanism of ATO's carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer.

Zhang L, Hu J, Li J, et al.
Long noncoding RNA LINC-PINT inhibits non-small cell lung cancer progression through sponging miR-218-5p/PDCD4.
Artif Cells Nanomed Biotechnol. 2019; 47(1):1595-1602 [PubMed] Related Publications
Long noncoding RNA, long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT) was showed to be involved in cancer development. However, the biological effect of LINC-PINT on non-small cell lung cancer (NSCLC) remains unknown. Here, we aimed to investigate the role and underlying mechanism of LINC-PINT in NSCLC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the level of LINC-PINT in NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), flow cytometry, migration and transwell invasion assays were used to investigate cell proliferation, cell cycle, cell migration and invasion, respectively. The targets of LINC-PINT were verified by both luciferase reporter assay and RNA immunoprecipitation assay. Tumour xenografts were used to reveal the effect of LINC-PINT on tumourigenesis in vivo. We observed that LINC-PINT expression increased in both NSCLC tissues and cell lines. Function assays exhibited that LINC-PINT reduced NSCLC cell proliferation, cell cycle, cell migration and invasion in vitro. We also indicated that LINC-PINT mediated inhibitory effect on cell proliferation, cell cycle, cell migration and invasion by miR-208a-3p/programmed cell death 4 (PDCD4) in NSCLC cells. These findings indicated that LINC-PINT functions as a tumour-suppressor that exerts important regulatory roles in NSCLC progression by sponging miR-208a-3p/PDCD4.

Zuo J, Jiang Y, Zhang E, et al.
Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer.
Life Sci. 2019; 227:145-152 [PubMed] Related Publications
AIMS: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.
MAIN METHODS: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively. Cell viability was detected using CCK-8 assay. Cell apoptosis was determined by Hoechst33342 staining and AV-PI staining. Tumors bearing mice were administered with GQ by gavage, and/or with liposome CDO14 mediated siRNAs via tail intravenous injection. Expression levels of proteins and cytokines were detected by western blot and ELISA, respectively.
KEY FINDINGS: Liposome CDO14 could deliver siRNA to tumor effectively. Combination of GQ and siSuvi promoted the antiproliferation and pro-apoptosis effects of GQ or siSuvi to MCF-7 cells, and reduced the level of survivin and raised the level of caspase-7 in cells. GQ combining with siSuvi inhibited the growth of tumor, down-regulated the expression of survivin and up-regulated the expression of caspase-7 in tumor tissue. Similarly, GQ combining with siIL-10 inhibited the growth of tumor, decreased the level of IL-10 and increased the level of TNF-α. These results revealed that GQ enhanced the pro-apoptosis effect of siSuvi on tumor cells and the modulating effect of siIL-10 on tumor microenvironment.
SIGNIFICANCES: Synergistic anti-tumor effect of GQ and siRNAs against breast cancer proved that chemical drugs combining with siRNAs is a promising antitumor strategy.

Wang Y, Huang H, Li Y
Knocking down miR-384 promotes growth and metastasis of osteosarcoma MG63 cells by targeting SLBP.
Artif Cells Nanomed Biotechnol. 2019; 47(1):1458-1465 [PubMed] Related Publications
Osteosarcoma is a common malignant bone tumour in adolescents and old people, with highly invasive and metastatic features and poor prognosis. This study aimed to explore the role of miR-384 in osteosarcoma MG63 cells by targeting SLBP. Cell viability, migration and invasion, apoptosis, as well as apoptosis-related factors were evaluated by CCK-8 assay, Transwell assay, flow cytometer and Western blotting, respectively. Dual-luciferase reporter assay was used to determine the target of miR-384. SLBP level was analyzed using qRT-PCR and Western blotting. Important factors of MEK/ERK and PI3K/AKT signalling pathways were analyzed using Western blotting. We found that miR-384 was down-regulated in osteosarcoma tissue samples and cell lines (MG63, U2OS and OS732). miR-384 overexpression inhibited viability, migration and invasion, but promoted apoptosis of MG63 cells; whereas, miR-384 silence exhibited the contrary effects on MG63 cells. SLBP was a target of miR-384. Knockdown of SLBP reversed the promoting effect of miR-384 silence on cells, indicating that miR-384 silence promoted growth and metastasis of MG63 cells by up-regulating SLBP. In conclusion, knocking down miR-384 promoted the growth and metastasis of osteosarcoma MG63 cells by up-regulating SLBP. To conclude, miR-384-SLBP may be a potential therapeutic target for osteosarcoma therapy.

Xu J, Wang Y, Li Z, et al.
Ultrasound-Targeted Microbubble Destruction (UTMD) Combined with Liposome Increases the Effectiveness of Suppressing Proliferation, Migration, Invasion, and Epithelial- Mesenchymal Transition (EMT) via Targeting Metadherin (MTDH) by ShRNA.
Med Sci Monit. 2019; 25:2640-2648 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods. MATERIAL AND METHODS Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR. RESULTS The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line. CONCLUSIONS UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.

Ma L, Wang H, Li Z, et al.
Chemokine (C-C motif) ligand 18 is highly expressed in glioma tissues and promotes invasion of glioblastoma cells.
J Cancer Res Ther. 2019; 15(2):358-364 [PubMed] Related Publications
Objective: The objective of the study is to evaluate levels of chemokine (C-C motif) ligand 18 (CCL18) in human glioma tissues and effects of CCL18 on U251 glioma cells.
Materials and Methods: By using the real-time reverse transcription polymerase chain reaction and immunochemically histological staining, we determined the mRNA and protein levels of CCL18 in tissues of 60 patients with World Health Organization (WHO) Grades II, III and IV glioma and the normal brain. Cultured U251 glioma cells were incubated with CCL18 and then subjected to transwell. The scratch wound-healing and cell count kit (CCK-8) assays were performed to detect the possible effects of CCL18 on the cell invasion, migration, and proliferation.
Results: In the tissues of the normal brain (n = 10), glioma Grade II (n = 26), III (n = 18), and IV (n = 16), CCL18 mRNA expression levels were 1.00 ± 0.09, 6.02 ± 1.26, 26.35 ± 3.98, and 112.21 ± 13.25 fold, respectively (P < 0.01); the percentage of CCL18-positive glioma cells was 0%, 58.8%, 70.0%, and 100% in the normal brain, glioma WHO Grade II, III, and IV, respectively (P < 0.01). Different concentrations of CCL18 (0, 5, and 10 ng/ml) enhanced the of U251 glioma cell invasion in 24 h transwell assays [from 43.5 ± 8.3 to 202.0 ± 18.5 and 279.7 ± 18.6 cells (P < 0.01)], increased the cell migration quantified by comparing the areas of the scratch (pixel) [at 12 h, 498.4 ± 75.3, 381.3 ± 21.4, and 347.7 ± 14.2; at 24 h, 299.5 ± 15.3, 284.6 ± 7.8, and 237.3 ± 20.6 (P < 0.05)], and significantly increased the cell growth in CCK-8 assay [from 1.000 ± 0.019-1.260 ± 0.094 and 2.070 ± 0.138 fold in CCL18, respectively (n = 20/each group) (P < 0.01)].
Conclusion: We have found that CCL18 is highly expressed in glioma tissues and enhances the invasion, migration, and proliferation of U251 glioma cells. Therefore, CCL18 may be a potential biomarker for detecting and grading human glioma.

Liu T, Jin L, Lu W, et al.
Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo.
J Exp Clin Cancer Res. 2019; 38(1):148 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.
METHODS: Six human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation assay; cell cycle and apoptosis were evaluated by flow cytometry; cell migration and invasion were measured by wound healing and transwell invasion assays respectively; protein expression was by detected by Western blot.
RESULTS: The growth inhibition effect of pemetrexed combined with icotinib on NSCLC cells were schedule-dependent in vitro and in vivo. Treatment with pemetrexed followed by icotinib (P-I) had significantly stronger anticancer ability than treatment with icotinib followed by pemetrexed (I-P) and concomitant treatment with pemetrexed and icotinib (P + I). Cell cycle analysis revealed that pemetrexed blocked cells in S phase, whereas icotinib arrested cells in G1 phase. We also found that icotinib markedly enhanced the pro-apoptotic activity of pemetrexed via cytochrome-C/Caspase/Bcl-2 signaling pathway. In addition, our results showed that pemetrexed alone increased the levels of p-EGFR, p-AKT and p-MAPK, which were inhibited by icotinib. Finally, we showed that the washout period of icotinib was no less than 96 h.
CONCLUSIONS: Sequential treatment of NSCLC cells with pemetrexed followed by icotinib had powerful antiproliferative effect, and it could become a novel effective combination therapy for NSCLC patients.

He C, Sun Z, Hoffman RM, et al.
P-Glycoprotein Overexpression Is Associated With Cisplatin Resistance in Human Osteosarcoma.
Anticancer Res. 2019; 39(4):1711-1718 [PubMed] Related Publications
BACKGROUND/AIM: Osteosarcoma (OS) is a diagnosed primary cancer of the bone. Despite the great advances that have been made during the past decades in OS therapy, drug resistance and tumor recurrence are still major problems. It is urgent to find novel strategies to overcome drug resistance in order to prolong the survival time of OS patients.
MATERIALS AND METHODS: Cell viability was investigated by the cell count kit-8 (CCK-8) and colony formation assays. P-Glycoprotein (P-gp) expression was analyzed by RT-qPCR and western blot. A xenograft mouse model was used to identify the synergistic efficacy of a P-gp inhibitor with cisplatin. Student's t-test was used to determine statistically significant differences.
RESULTS: P-gp expression levels were associated with cisplatin efficacy in OS patients. OS cells with higher P-gp expression were more resistant to cisplatin. Knockdown or inhibition of P-gp sensitized OS cells to cisplatin.
CONCLUSION: Down-regulating the expression of P-gp in OS maybe a promising strategy to overcome cisplatin resistance.

Zhou M, Li W
Ent-Dihydrotucumanoic acid promotes apoptosis in PC-3 human prostate cancer cells.
Cell Mol Biol (Noisy-le-grand). 2019; 65(3):114-118 [PubMed] Related Publications
Prostate cancer (PC) has become a disease that pose a serious threat to men's health and life. In recent years, due to the changes of environment, lifestyle and other factors, the incidence of PC has been increasing rapidly in recent years, which is a serious threat to men's health. Ent-Dihydrotucumanoic Acid (DTA) is a compound isolated from Asteraceae of gymnosperms, which has many pharmacological effects. The effect of DTA on the growth of tumor cell line was studied by CCK-8 method, mitochondrial membrane potential and apoptosis were detected by flow cytometry, apoptosis-related genes were detected by Western blot assay, and the absorptivity of Caspase-3 and Caspase-9 was measured by spectrophotometer. It was found that DTA induces apoptosis of human prostate cancer cell line PC3 through mitochondrial pathway, thus preventing the development of prostate cancer. It lays the experimental foundation for the further development of DTA.

Yuan X, Liu J, Ye X
Effect of miR-200c on the proliferation, migration and invasion of breast cancer cells and relevant mechanisms.
J BUON. 2019 Jan-Feb; 24(1):61-67 [PubMed] Related Publications
PURPOSE: The current study aimed to explore the effect of miR-200c on the proliferation, migration and invasion of breast cancer cells and its relevant mechanisms.
METHODS: Cell counting kit-8 (CCK-8), scratch wound healing assay and Transwell assay were performed after upregulation of miR-200c to detect the capabilities of proliferation, migration and invasion of MCF-7 breast cancer cells. Also, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were carried out to determine the expression levels of fucosyltransferase-4 (FUT4) and relevant genes in PI3K/AKT signaling pathways.
RESULTS: miR-200c upregulation in MCF-7 cells decreased the capabilities of proliferation, migration and invasion in MCF-7 cells. MiR-200c could regulate the level of FUT4 in MCF-7 cells, and might affect the cell proliferation, migration and invasion through PI3K/AKT signaling pathway.
CONCLUSIONS: The results of this study indicated that miR-200c might serve as a new target in the diagnosis and treatment of breast cancer. MiR-200c regulated the expression of FUT4, and affected the biological behaviors of breast cancer MCF-7 cells, such as proliferation, migration and invasion.

Deng L, Liu G, Zheng C, et al.
Circ-LAMP1 promotes T-cell lymphoblastic lymphoma progression via acting as a ceRNA for miR-615-5p to regulate DDR2 expression.
Gene. 2019; 701:146-151 [PubMed] Related Publications
Circular RNAs (circRNAs) act as pivotal functions in tumor progression. Nevertheless, the functions and mechanism of circRNAs in T-cell lymphoblastic lymphoma (T-LBL) remain unclear. In this work, we first screened the differentially expressed circRNAs between T-LBL tissues and normal infantile thymus and circ-LAMP1 was identified the highest expressed circRNA in cancerous tissues. qRT-PCR further verified its upregulation in T-LBL tissues and cell lines. Cell counting kit-8 (CCK-8) experiment proved the cell proliferation-promoting role of circ-LAMP1. This effect is partially dependent on its inhibition on cell apoptosis proved by flow cytometric assay. Dual-luciferase reporter system further identified that miR-615-5p could be sponged by circ-LAMP1 and discoidin domain receptor tyrosine kinase 2 (DDR2) 3'-UTR is the direct target of miR-615-5p. Rescue assays demonstrated that the biological function of circ-LAMP1 is partly attributed to the modulation of miR-615-5p/DDR2 signaling. In summary, these findings documented that circ-LAMP1 might be an oncogene in T-LBL, which might be useful in developing promising therapies for T-LBL.

Ding Q, Li X, Sun Y, Zhang X
Schizandrin A inhibits proliferation, migration and invasion of thyroid cancer cell line TPC-1 by down regulation of microRNA-429.
Cancer Biomark. 2019; 24(4):497-508 [PubMed] Related Publications
OBJECTIVE: Schizandrin A (SchA) exerts anticancer potential. However, the effects of SchA on thyroid cancer (TC) have not been clear illuminated. Therefore, we investigated the effects of SchA on TC cell line TPC-1 and the underlying mechanisms.
METHODS: TPC-1 cells were treated with SchA and/or transfected with miR-429 mimic, anti-miR-429 and their corresponding negative controls (NC). Cell viability, proliferation, migration, invasion and cell apoptosis were examined by CCK-8 assay, bromodeoxyuridine, modified two-chamber migration assay, Millicell Hanging Cell Culture and flow cytometry analysis, respectively. The expression of miR-429, p16, Cyclin D1, cyclin-dependent kinases 4 (CDK4), matrix metalloprotein (MMP)-2, MMP-9 and Vimentin was detected by qRT-PCR. All protein expression was examined by western blot.
RESULTS: SchA inhibited cell proliferation, metastasis and induced cell apoptosis. Moreover, SchA negatively regulated miR-429 expression. Treatment with miR-429 mimic and SchA reversed the results led by SchA and NC. Furthermore, the phosphorylation β-catenin, mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK) were statistically down-regulated by SchA while co-treatment with miR-429 mimic and SchA led to the opposite trend. Moreover, miR-429 knockdown showed contrary results.
CONCLUSION: SchA inhibits cell proliferation, migration, invasion and inactivates Wnt/β-catenin and MEK/ERK signaling pathways by down regulating miR-429.

Li XF, Zhao GQ, Li LY
Ginsenoside impedes proliferation and induces apoptosis of human osteosarcoma cells by down-regulating β-catenin.
Cancer Biomark. 2019; 24(4):395-404 [PubMed] Related Publications
BACKGROUND: Osteosarcoma (OS) is the most commonly occurred primary bone malignancy with high incident rates among children and adolescents. In pharmacologic treatment, the drug ginsenoside has been shown to exert anticancer effects on several malignant diseases. The purpose of this research was to investigate the effect of ginsenoside on the apoptosis and proliferation of human OS MG-63 and Saos-2 cells by regulating the expression of β-catenin.
METHODS: Human OS MG-63 and Saos-2 cells were assigned into control group, and four groups with treatment by varying concentrations (12.5 μg/mL, 25 μg/mL, 50 μg/mL and 100 μg/mL) of ginsenoside, respectively. Cell growth after treatment was observed through cell slides. The proliferation rate of MG-63 and Saos-2 cells in each group was detected by CCK-8. After cell transfection at 48 h, cell cycle and cell apoptosis were detected by FITC-Annexin V staining and flow cytometry. The protein and mRNA expressions of β-catenin, Cyclin D1, Bcl-2, Bax and cleaved caspase-3 were detected by RT-qPCR and western blot analysis.
RESULTS: With increased exposure and concentration of ginsenoside, the cell density, total cell numbers and the absorbance of MG-63 and Saos-2 cells gradually decreased. FITC-Annexin V and FITC-Annexin V/PI staining demonstrated that the cell proportion at S phase decreased, whereas the total apoptotic rate of MG-63 and Saos-2 cells was increased. Furthermore, RT-qPCR and western blot analysis highlighted a gradual decrease in protein and mRNA expressions of β-catenin, Bcl-2 and Cyclin D1, while an elevation in those of Bax and cleaved caspase-3.
CONCLUSION: The results of this study demonstrate that ginsenoside inhibits proliferation and promotes apoptosis of human OS MG-63 and Saos-2 cells by reducing the expressions of β-catenin, Bcl-2 and Cyclin D1 and increasing the expression of Bax and cleaved caspase-3.

Liu F, Yin R, Chen X, et al.
Over-expression of miR-206 decreases the Euthyrox-resistance by targeting MAP4K3 in papillary thyroid carcinoma.
Biomed Pharmacother. 2019; 114:108605 [PubMed] Related Publications
PURPOSE: microRNAs (miRNAs) play a critical role in drug resistance of multiple cancers including papillary thyroid carcinoma (PTC), indicating the potential of miRNAs as chemoresistance regulators in cancer treatment. The aim of this paper is to explore the relationship between miR-206 and chemoresistance of PTC.
METHODS: qRT-PCR was conducted to examine the expression of miR-206 in PTC tissues, parental and TPC-1/euthyrox. The CCK-8 assay, EdU assay and flow cytometry were performed to test cells viability, proliferation and apoptosis, respectively. Luciferase reporter assay was used to confirm the potential target of miR-206. Western blotting analysis was performed to evaluate the expressions of related-proteins.
RESULTS: miR-206 was significantly down-regulated in PTC tissues, parental and TPC-1/euthyrox. Moreover, the expression of miR-206 was exceptionally lower in TPC-1/euthyrox cells than that in TPC-1 cells. Furthermore, we found that over-expression of miR-206 could notably decrease the IC
CONCLUSION: miR-206 contributed to euthyrox resistance in PTC cells through blockage p38 and JNK signaling pathway by targeting MAP4K3, providing a potential therapeutic application for the treatment of patients with euthyrox-resistant PTC in the further.

Shen Z, Liao X, Shao Z, et al.
Short-term stimulation with histone deacetylase inhibitor trichostatin a induces epithelial-mesenchymal transition in nasopharyngeal carcinoma cells without increasing cell invasion ability.
BMC Cancer. 2019; 19(1):262 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Epithelial-mesenchymal transition (EMT) may be one of the reasons for the failure in some clinical trials regarding histone deacetylase inhibitors (HDACIs)-treated solid tumors. We investigated the effects of a pan-HDACI trichostatin A (TSA) on the proliferation and EMT of nasopharyngeal carcinoma (NPC) cells.
METHODS: Poorly-differentiated NPC cell line CNE2 and undifferentiated C666-1 were treated with various concentrations of TSA, the cell viability was assessed by CCK-8 assay, the morphology was photographed, and the mRNA level of HDACs was assessed by semiquantitative PCR. After determination the cell cycle distributions, cells were subjected to western blotting analysis of cell cycle and EMT-associated genes expression. And the changes in migration ability were assessed by transwell migration assay and scratch wound healing assay. Finally, histone deacetylases activator ITSA-1 was used to assess the reverse of TSA-induced changes in NPC cells.
RESULTS: TSA inhibited the proliferation of CNE2 and C666-1 cells in a concentration-dependent manner and arrested the cell cycle at G1 phases. TSA reduced PCNA, cyclin D1, cyclin E1, CDK2, p16 and p21 expressions and stimulated CDK6 levels. TSA stimulation for 48 h could effectively induce the EMT in CNE2 and C666-1 cells, which showed an increase of spindle-like cells and promoted expression of Vimentin and Snail1 expression in a concentration-dependent manner. Surprisingly, this short period of TSA treatment that induced EMT also impeded the migration ability of CNE2 and C666-1 cells. Interestingly, ITSA-1 rescued TSA-impeded CNE2 and C666-1 cells' proliferation, migration and HDACs expression, also re-induced the cells to turn into epithelial cell phenotypes.
CONCLUSIONS: These results indicate that short-term stimulation of TSA effectively inhibits cell proliferation and induce EMT-like changes in NPC cells but not increase its invasion ability.

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