This section is being extended during 2015.

MicroRNAs involved in Cancer

NameAliasesLocationTarget(s)Main EffectPublicationsDetail
miR-21MIRN21, miR-21, miRNA21, hsa-mir-2117q23.1PDCD4,  PTEN,  RECK,  TIMP3,  and 34 other genesoncogenic 1816View
miR-126MIRN126, mir-126, miRNA1269q34.3VEGFA,  PIK3R2,  CXCL2,  SOX2,  and 5 other genestumor-suppressive 317View
miR-122MIR122A, MIRN122, mir-122, MIRN122A, miRNA122, miRNA122A, hsa-mir-12218q21.31IGF1R,  PTTG1IP,  CDK4,  ADAM10,  and 7 other genestumor-suppressive 283View
let-7bLET7B, let-7b, MIRNLET7B, hsa-let-7b22q13.31CYP2J2,  CCND1,  PRDM1tumor-suppressive 163View
let-7cLET7C, let-7c, MIRNLET7C, hsa-let-7c21q21.15088,  BCL2L1,  CASP3,  SOCS1tumor-suppressive 135View
miR-107MIRN107, miR-10710q23.31DICER1,  SUZ12,  KLF4,  NFIA,  and 6 other genestumor-suppressive 119View
miR-10aMIRN10A, mir-10a, miRNA10A, hsa-mir-10a17q21.32DDX11,  RB1CC1,  SRSF1,  KLF4,  and 4 other genesoncogenic 98View
let-7iLET7I, let-7i, MIRNLET7I, hsa-let-7i12q14.1PGRMC1tumor-suppressive 76View
miR-127MIRN127, mir-127, miRNA12714q32.2CXCL12tumor-suppressive 63View
miR-127-3pMIRN127, mir-127, miRNA12714q32.263View
let-7dLET7D, let-7d, MIRNLET7D, hsa-let-7d9q22.32PBX3tumor-suppressive 57View
let-7eLET7E, let-7e, MIRNLET7E, hsa-let-7e19q13.41CCND1,  MYCNtumor-suppressive 51View
let-7gLET7G, let-7g, MIRNLET7G, hsa-let-7g3p21.1GAB2,  COL1A2,  BCL2L1,  FN1,  and 1 other genestumor-suppressive 44View
miR-1290MIRN1290, hsa-mir-12901p36.13KIF13B41View
miR-124aMIR124A, MIR124A1, MIRN124-1, MIRN124A1, mir-124-18p23.1CDK6tumor-suppressive 39View
miR-1271MIRN1271, hsa-mir-12715q35.2GPC3tumor-suppressive 24View
miR-1297MIRN1297, mir-1297, hsa-mir-129713q14.3TRIB2,  PTENtumor-suppressive 19View
miR-1301MIRN1301, mir-1301, hsa-mir-13012p23.3tumor-suppressive 17View
miR-1258MIRN1258, mir-1258, hsa-mir-12582q31.3HPSEtumor-suppressive 10View
miR-1226MIRN1226, mir-1226, hsa-mir-12263p21.31MUC1tumor-suppressive 4View
miR-1256MIRN1256, hsa-mir-12561p36.12TRIM68tumor-suppressive 3View

Latest Publications

Xu P, Xia T, Ling Y, Chen B
MiRNAs with prognostic significance in multiple myeloma: A systemic review and meta-analysis.
Medicine (Baltimore). 2019; 98(33):e16711 [PubMed] Related Publications
BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM.
METHODS: A meta-analysis was performed to estimate the pooled hazard ratios and their corresponding 95% confidence intervals for the associations between levels of miRNA expression (predictive factors) and outcomes in patients with MM. We systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases (final search conducted January 1, 2018) to identify eligible studies. Eligible studies were included by certain inclusion and exclusion criteria, whose quality was assessed by Newcastle-Ottawa Scale.
RESULTS: After performing the literature search and review, 10 relevant studies, including 1214 cases, were identified. The results of our meta-analysis revealed that upregulated miR-92a level and downregulated miR-16, miR-25, miR-744, miR-15a, let-7e, and miR-19b expression were associated with poor prognosis in MM.
CONCLUSIONS: This study identified miRNAs could serve as potential prognostic biomarkers in MM. Given the limited research available, the clinical application of these findings has yet to be verified.

Guo Y
Clinical significance of serum MicroRNA-203 in patients with acute myeloid leukemia.
Bioengineered. 2019; 10(1):345-352 [PubMed] Related Publications
This study aimed to detect serum miR-203 expression levels in AML and explore its potential clinical significance. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure the serum miR-203 levels in 134 patients with AML and 70 healthy controls. The results demonstrated that serum miR-203 expression was significantly reduced in AML patients compared with healthy controls. Receiver operating characteristic curve (ROC) analysis revealed miR-203 could distinguish AML cases from normal controls. Low serum miR-203 levels were associated with worse clinical features, as well as poorer overall survival and relapse free survival of AML patients. Moreover, multivariate analysis confirmed low serum miR-203 expression to be an independent unfavorable prognostic predictor for AML. The bioinformatics analysis showed that the downstream genes and pathways of miR-203 was closely associated with tumorigenesis. Downregulation of miR-203 in AML cell lines upregulated the expression levels of oncogenic promoters such as CREB1, SRC and HDAC1. Thus, these findings demonstrated that serum miR-203 might be a promising biomarker for the diagnosis and prognosis of AML.

Ye H, Zhu W, Mei L, Lu Z
Prognostic and clinicopathologic significance of MicroRNA-125a-5p in cancers: A meta-analysis.
Medicine (Baltimore). 2019; 98(31):e16685 [PubMed] Related Publications
The aim of the study was to estimate the prognostic and clinicopathologic significance of miR-125a-5p in human cancers. Eligible studies were obtained from PubMed, Embase, and the Cochrane Library. Combined hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the prognostic and clinicopathologic value of miR-125a-5p. In pan-cancer, high miR-125a-5p expression was associated with better overall survival (OS) (HR = 0.459, 95% confidence interval [CI]: 0.369-0.57, P < .001), and disease-free survival (HR = 0.343, 95% CI: 0.237-0.496, P < .001). Furthermore, favorable OS was also found in lung cancer (HR = 0.343, 95% CI: 0.228-0.517, P < .001) and gastric cancer (HR = 0.341, 95% CI: 0.160-0.725, P = .005) patients with high miR-125a-5p expression. Besides, high miR-125a-5p expression was correlated with early stage (OR = 0.413, 95% CI: 0.228-0.749, P = .004) and negative lymph node metastasis (OR = 0.262, 95% CI: 0.073-0.941, P = .04) in gastric cancer, and was linked with better tumor differentiation in pan-cancer (OR = 1.623, 95% CI: 1.064-2.476, P = .025) and lung cancer (OR = 2.371, 95% CI: 1.358-4.141, P = .002). In conclusion, miR-125a-5p is a tumor suppressor with prognostic and clinicopathologic values for human cancer, and miR-125a-5p overexpression predicted favorable prognosis, early stage, negative lymph node metastasis, and better tumor differentiation. More research should be conducted to test these results.

Valentini V, Zelli V, Gaggiano E, et al.
MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.
Anticancer Res. 2019; 39(8):4085-4093 [PubMed] Related Publications
BACKGROUND/AIM: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinical-pathological factors.
MATERIALS AND METHODS: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR-211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR.
RESULTS: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm

Li Z, Tan H, Zhao W, et al.
Integrative analysis of DNA methylation and gene expression profiles identifies MIR4435-2HG as an oncogenic lncRNA for glioma progression.
Gene. 2019; 715:144012 [PubMed] Related Publications
Long noncoding RNAs (lncRNAs) have been shown to play an important role in tumor biogenesis and prognosis. The glioma is a grade classified cancer, however, we still lack the knowledge on their function during glioma progression. While previous studies have shown how lncRNAs regulate protein-coding gene epigenetically, it is still unclear how lncRNAs are regulated epigenetically. In this study, we firstly analyzed the RNA-seq data systematically across grades II, IV, and IV of glioma samples. We identified 60 lncRNAs that are significantly differentially expressed over disease progression (DElncRNA), including well-known PVT1, HOTAIR, H19 and rarely studied CARD8-AS, MIR4435-2HG. Secondly, by integrating HM450K methylation microarray data, we demonstrated that some of the lncRNAs are epigenetically regulated by methylation. Thirdly, we developed a DESeq2-GSEA-ceRNA-survival analysis strategy to investigate their functions. Particularly, MIR4435-2HG is highly expressed in high-grade glioma and may have an impact on EMT and TNFα signaling pathway by functioning as a miRNA sponge of miR-125a-5p and miR-125b-5p to increase the expression of CD44. Our results revealed the dynamic expression of lncRNAs in glioma progression and their epigenetic regulation mechanism.

Zhu X, Tan J, Liang Z, Zhou M
Comprehensive analysis of competing endogenous RNA network and 3-mRNA signature predicting survival in papillary renal cell cancer.
Medicine (Baltimore). 2019; 98(30):e16672 [PubMed] Related Publications
Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to exert significant roles in regulating the expression of mRNAs by sequestering and binding miRNAs. To elucidate the functional roles and regulatory mechanism of lncRNAs in papillary renal cell cancer (pRCC), we conducted a comprehensive analysis of ceRNA network and constructed a mRNA signature to predict prognosis of pRCC.We collected mRNAs and lncRNAs expression profiles of 289 pRCC samples and 32 normal renal tissues, and miRNA expression profiles of 292 pRCC samples and 34 normal samples from The Cancer Genome Atlas (TCGA) database. Differential expressions of RNAs were evaluated by the "edgeR" package in R. Functional enrichment analysis of DEmRNA was performed by DAVID 6.8 and KEGG, while PPI network of top 200 DEmRNAs was conducted using the STRING database. The univariate and multivariate Cox regression were conducted to figure out the candidate DEmRNAs with predictive values in prognosis. Receiver operator characteristic (ROC) curve estimation was performed to achieve the area under the curve (AUC) of the ROC curve to judge mRNA-associated prognosic model. A ceRNA network was established relying on the basis of combination of lncRNA-miRNA interactions and miRNA-mRNA interactions.A total of 1928 DEmRNAs, 981 DElncRNAs, and 52 DEmiRNAs were identified at significance level of |log2Fold Change |>2 and adjusted P-value < .01. A 3-mRNA signatures consisting of ERG, RRM2, and EGF was constructed to predict survival in pRCC. Moreover, a pRCC-associated ceRNA network was constructed, with 57 lncRNAs, 11 miRNAs, and 28 mRNAs.Our study illustrated the regulatory mechanism of ceRNA network in papillary renal cancer. The identified mRNA signatures could be used to predict survival of pRCC.

Zhou Y, Shen S
MiR-520f acts as a biomarker for the diagnosis of lung cancer.
Medicine (Baltimore). 2019; 98(30):e16546 [PubMed] Related Publications
Lung cancer is a malignant tumor with high morbidity and mortality. Early diagnosis remains a great challenge for the cancer. In this study, we aimed to explore diagnostic performance of serum microRNA-520f (miR-520f) in lung cancer.Serum specimens were collected from 139 lung cancer patients and 76 healthy volunteers. Relative expression level of serum miR-520f was detected adopting quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was applied to evaluate the association of miR-520f with clinical parameters of the patients. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic value of miR-520f in lung cancer.Serum miR-520f was down-regulated in lung cancer patients compared with healthy group (P <.001). Moreover, the expression of miR-520f was significantly associated with advanced TNM stage (P = .031) and metastasis (P = .002). The area under the curve (AUC) value of ROC curve was 0.888, suggesting that miR-520f could be a diagnostic biomarker for lung cancer. The cut-off value of serum miR-520f for lung cancer diagnosis was 1.815, with a sensitivity of 79.9% and a specificity of 84.2%.Serum miR-520f was down-regulated in lung cancer patients, and may be a candidate biomarker for non-invasive screening of the disease.

Liu JB, Yan YJ, Shi J, et al.
Upregulation of microRNA-191 can serve as an independent prognostic marker for poor survival in prostate cancer.
Medicine (Baltimore). 2019; 98(29):e16193 [PubMed] Related Publications
MicroRNA-191 (miR-191) has been identified as being upregulated in several types of cancers, and plays the role of oncogene. The expression of miR-191 has been found to be upregulated in prostate cancer tissues as well as cell lines. In this study, we analyzed the correlation of miR-191 expression with clinicopathologic factors and prognosis in prostate cancer.Prostate cancer tissue samples and adjacent normal prostate tissue samples were collected from 146 patients who underwent laparoscopic radical prostatectomy between April 2013 and March 2018. Student two-tailed t-test was used for comparisons of 2 independent groups. The relationships between miR-191 expression and different clinicopathological characteristics were evaluated using the Chi-squared test. Kaplan-Meier survival plots and log-rank tests were used to assess the differences in overall survival of the different subgroups of prostate cancer patients.miR-191 expression was significantly higher in prostate cancer tissues compared with normal adjacent prostate tissues (P < .001). miR-191 expression was observed to be significantly correlated with Gleason score (P < .001), pelvic lymph node metastasis (P = .006), bone metastases (P < .001), and T stage (P = .005). Kaplan-Meier analysis showed that patients with higher levels of miR-191 had significantly poorer survival than those with lower expression of this miRNA in prostate cancer patients (log rank test, P = .011). Multivariate analysis revealed that miR-191 expression (hazard ratio [HR] = 2.311, 95% confidence interval, [CI]: 1.666-9.006; P = .027) was independently associated with the overall survival of prostate cancer patients.Our results demonstrated that miR-191 might serve as an independent prognostic indicator for prostate cancer patients.

Pei Y, Yao Q, Li Y, et al.
microRNA-211 regulates cell proliferation, apoptosis and migration/invasion in human osteosarcoma via targeting EZRIN.
Cell Mol Biol Lett. 2019; 24:48 [PubMed] Free Access to Full Article Related Publications
Background: In recent years, microRNA-211 (miR211) has been considered as a tumor suppressor in multiple malignancies. However, the function of miR211 in human osteosarcoma has not been explored intensively so far. In this study, the relationship between miR211 and EZRIN was analyzed in human osteosarcoma.
Methods: The expression levels of miR211 and EZRIN were measured in both human osteosarcoma cells and tissues. The direct regulatory relationship between miR211 and EZRIN was evaluated using dual-luciferase assay. The effect of miR211 and EZRIN overexpression on cell proliferation, migration/invasion, and apoptosis was detected.
Results: The expression of miR211 was obviously lower in osteosarcoma tissues than paracancerous tissues. EZRIN was identified as the direct target of miR211, and up-regulation of miR211 increased the percentage of cell apoptosis, and suppressed cell proliferation as well as cell migration/invasion via directly regulating EZRIN.
Conclusions: Our study indicated that miR211 has an important role in the development and progress of osteosarcoma, and it might become a novel target in the diagnosis and treatment of human osteosarcoma.

Liu L, Qi X, Gui Y, et al.
Overexpression of circ_0021093 circular RNA forecasts an unfavorable prognosis and facilitates cell progression by targeting the miR-766-3p/MTA3 pathway in hepatocellular carcinoma.
Gene. 2019; 714:143992 [PubMed] Related Publications
Increasing studies have demonstrated the important roles of circular RNAs (circRNAs) in human malignancies. Nevertheless, the molecular mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) are still not fully understood. In the present study, we evaluated circ_0021093 expression in 82 pairs of HCC tissues and 5 cell lines by qRT-PCR. The clinical implications of circ_0021093 were evaluated. In addition, the viability, apoptosis, migration and invasion capacities of different HCC cells were evaluated by gain-/loss-of-function experiments. Target prediction and dual-luciferase reporter experiments were performed to identify the molecular mechanisms of circ_0021093. Upregulation of circ_0021093 was found in HCC tumor samples and cells. Additionally, upregulated circ_0021093 was related to adverse clinical characteristics and an unfavorable prognosis. Furthermore, downregulated circ_0021093 attenuated cell growth, migration and invasion but increased cell apoptosis. By contrast, ectopically expressed circ_0021093 enhanced the abovementioned malignant biological behaviors. For mechanism exploration, circ_0021093 sponges of miR-766-3p were used in HCC cells. In addition, we found that metastasis-associated protein 3 (MTA3) was a direct target of miR-766-3p and that the oncogenic function of circ_0021093 was partly dependent on the miR-766-3p/MTA3 axis according to rescue assays. In conclusion, the circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC.

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.

Li Y, He S, Zhan Y, et al.
microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5.
DNA Cell Biol. 2019; 38(8):840-848 [PubMed] Related Publications
microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (

Yang X, Li X, Quan X, et al.
Association Between Two Polymorphisms in the Promoter Region of miR-143/miR-145 and the Susceptibility of Lung Cancer in Northeast Chinese Nonsmoking Females.
DNA Cell Biol. 2019; 38(8):814-823 [PubMed] Related Publications
Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723,

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.

Chen Z, Ou H, Wu H, et al.
Role of microRNA in the Pathogenesis of Polycystic Ovary Syndrome.
DNA Cell Biol. 2019; 38(8):754-762 [PubMed] Related Publications
Polycystic ovary syndrome (PCOS) is the most typical metabolic syndrome in women of reproductive age, with a high prevalence and an increased risk of long-term complications. PCOS mainly manifests as hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovaries, in addition to being relevant to infertility, insulin resistance (IR), obesity, lipid abnormalities, and chronic low-grade inflammation. The etiology of this syndrome remains largely unknown. microRNAs (miRNAs), small, noncoding RNAs (nearly 22 nucleotides long), regulate gene expression at the posttranscriptional level. Abnormal miRNA levels are closely associated with the occurrence of diseases, such as diabetes, cancers, and atherosclerosis, and miRNAs can be used as predictors and diagnostic biomarkers for cancer. Interestingly, the roles of miRNAs in PCOS pathology have attracted considerable attention in recent years. Research has established that alterations in miRNA expression in women with PCOS compared with healthy women may act as noninvasive biomarkers and new therapeutic targets in PCOS. This article aims to summarize the latest research on the relationship between miRNAs and the clinical manifestations of PCOS while also providing a few mechanisms based on previous studies. Understanding the relationship between miRNAs and PCOS will provide guidance for researchers to further explore the complexity and heterogeneity of PCOS.

Sun SQ, Ren LJ, Liu J, et al.
Sevoflurane inhibits migration and invasion of colorectal cancer cells by regulating microRNA-34a/ADAM10 axis.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Sevoflurane is frequently used volatile anesthetic in cancer surgery. It has been suggested that treatment with sevoflurane could suppress migration and invasion of several human cancer cells in vitro. However, the effects of sevoflurane on colorectal cancer (CRC) remains largely unclear. In this study, CRC HCT116 and SW480 cells were treated by various concentrations of sevoflurane. MTT assay and Transwell assay were applied to evaluate the cell viability, migration and invasion abilities of CRC cell lines, respectively. Real-time quantitative PCR (RT-qPCR) was used to examine the expression level of miR-34a, and western blot assay was employed to detect the protein level of ADAM10. The target interaction between miR-34a and ADAM10 was verified through bioinformatics analysis, luciferase reporter gene assay system. We found Aberrant inhibitory effects induced by sevoflurane on the cell viability, migration and invasion abilities of HCT116 and SW480 cells in a dose-dependent manner were observed. Up-regulation of miR-34a strikingly suppressed the cell proliferation, migration and invasion abilities of the two cell lines. Sevoflurane could facilitate the miR-34a expression and its suppressor effects on CRC cells was reversed by pre-treatment with miR-34a inhibitors. ADAM10 was identified as a downstream gene of miR-34a, and down-regulated by miR-34a. Overexpression of ADAM10 reverted both miR-34a and sevoflurane-induced repression in the cell proliferation, migration and invasion abilities of CRC cells. Our data showed Sevoflurane inhibits the migration and invasion of colorectal cancer cells by regulating microRNA-34a/ADAM10 axis.

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.

Fasihi A, Soltani BM, Ranjbaran ZS, et al.
Hsa-miR-942 fingerprint in colorectal cancer through Wnt signaling pathway.
Gene. 2019; 712:143958 [PubMed] Related Publications
The Wnt signaling pathway has been identified for its function in carcinogenesis and embryonic development. It is known to play a vital role in the initiation and development of colorectal cancer (CRC). Therefore, it is of great importance for CRC research to illuminate the mechanisms which regulate Wnt pathway activity. Here, we intended to examine the effect of hsa-miR-942 (miR-942) on the Wnt signaling activity, cell cycle progression, and its expression in CRC tissues. RT-qPCR results indicated that miR-942 is significantly upregulated in colorectal cancer. Then, overexpression of miR-942 promoted, whereas its inhibition decreased the Wnt signaling activity, detected by RT-qPCR and Top/Fop flash assay. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules indicated that miR-942 applies its effect to the β-catenin degradation complex level. Then, RT-qPCR and dual luciferase assay showed that miR-942 upregulated Wnt signaling through direct targeting of APC, which is a tumor suppressor in Wnt signaling pathway. Furthermore, the western blotting analysis indicated that β.catenin, as a main member of Wnt signaling pathway is upregulated following the overexpression of miR-942. Finally, miR-942 overexpression resulted in cell cycle progression in SW480 cells. Taken together, our findings established an oncogenic role for miR-942 in CRC and indicated that this miRNA might be a crucial target for CRC therapy.

Nappi L, Nichols C
MicroRNAs as Biomarkers for Germ Cell Tumors.
Urol Clin North Am. 2019; 46(3):449-457 [PubMed] Related Publications
Two clusters of microRNAs have been discovered highly expressed by seminoma and nonseminoma germ cell tumors. They are secreted in blood of patients with testicular germ cell tumors and can be extracted from the serum or plasma and quantified by real-time-polymerase chain reaction. Results have confirmed the feasibility of the technique and demonstrated that sensitivity and specificity of those microRNAs in detecting viable germ cell tumors are higher than with current methods. If operation characteristics are confirmed in larger studies, those microRNAs will be valuable to manage equivocal clinical scenarios characterized by high uncertainty and high risk of over-treatment or under-treatment.

Zhong X, Huang G, Ma Q, et al.
Identification of crucial miRNAs and genes in esophageal squamous cell carcinoma by miRNA-mRNA integrated analysis.
Medicine (Baltimore). 2019; 98(27):e16269 [PubMed] Free Access to Full Article Related Publications
Esophageal squamous cell carcinoma (ESCC) is a malignancy that severely threatens human health and carries a high incidence rate and a low 5-year survival rate. MicroRNAs (miRNAs) are commonly accepted as a key regulatory function in human cancer, but the potential regulatory mechanisms of miRNA-mRNA related to ESCC remain poorly understood.The GSE55857, GSE43732, and GSE6188 miRNA microarray datasets and the gene expression microarray datasets GSE70409, GSE29001, and GSE20347 were downloaded from Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network and functional modules were established using the STRING database and were visualized by Cytoscape. Kaplan-Meier analysis was constructed based on The Cancer Genome Atlas (TCGA) database.In total, 26 DEMs and 280 DEGs that consisted of 96 upregulated and 184 downregulated genes were screened out. A functional enrichment analysis showed that the DEGs were mainly enriched in the ECM-receptor interaction and cytochrome P450 metabolic pathways. In addition, MMP9, PCNA, TOP2A, MMP1, AURKA, MCM2, IVL, CYP2E1, SPRR3, FOS, FLG, TGM1, and CYP2C9 were considered to be hub genes owing to high degrees in the PPI network. MiR-183-5p was with the highest connectivity target genes in hub genes. FOS was predicted to be a common target gene of the significant DEMs. Hsa-miR-9-3p, hsa-miR-34c-3p and FOS were related to patient prognosis and higher expression of the transcripts were associated with a poor OS in patients with ESCC.Our study revealed the miRNA-mediated hub genes regulatory network as a model for predicting the molecular mechanism of ESCC. This may provide novel insights for unraveling the pathogenesis of ESCC.

Chen Y, Wu N, Liu L, et al.
Correlation between microRNA-21, microRNA-206 and estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 in breast cancer.
Clin Biochem. 2019; 71:52-57 [PubMed] Related Publications
BACKGROUND: Although the function of microRNA-21 and microRNA-206 in breast cancer cells have been investigated in vitro, their association with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are not reported.
METHODS: ER, PR, HER2, and Ki-67 staining pattern were utilized to classify 75 breast cancer patients recruited. The malignancy was predicted with tumor nodes metastases (TNM) classification. RT-qPCR was performed to detect the relative expression of ER, PR, and HER2 in tumor samples and microRNA-21 and microRNA-206 in the serum. Spearman's correlation analysis was used to determine the association between different molecules. According to the staining pattern, the breast cancer patients were classified into five types.
RESULTS: microRNA-21 was up-regulated in HER2 positive and Basal-like breast cancer types, while microRNA-206 was up-regulated in Luminal A and B types of breast cancer. microRNA-21 expression negatively correlated with the level of ER and PR but positively correlated with HER2 expression and tumor malignancy, while microRNA-206 showed the opposite trend. Neither microRNA-21 nor microRNA-206 showed any significant correlation with the age of the patients.
CONCLUSION: Both microRNA-21 and microRNA-206 closely correlate with ER, PR, and HER2 expression, which can be considered as clinical biomarkers.

Chen X
MiR-101 acts as a novel bio-marker in the diagnosis of bladder carcinoma.
Medicine (Baltimore). 2019; 98(26):e16051 [PubMed] Free Access to Full Article Related Publications
MiR-101 plays an important role in tumorigenesis. The aim of this study was to estimate diagnostic potential of serum miR-101 in bladder cancer.Serum level of miR-101 in 122 bladder cancer patients and 110 healthy volunteers was detected using quantitative real-time polymerase chain reaction method. The association between miR-101 expression and clinicopathological characteristic was analyzed via χ test. Then receiver operating characteristic (ROC) curve was plotted to evaluate diagnostic value of serum miR-101 in bladder cancer.MiR-101 expression was statistically down-regulated in bladder cancer patients compared to healthy controls. MiR-101 expression was significantly associated with TNM stage (P = .019), pathological grade (P = .006) and lymph node metastasis (P = .010). ROC analysis suggested that miR-101 had high value in discriminating between bladder cancer patients and healthy individuals with an AUC value of 0.884. The cut-off value for serum miR-101 in bladder cancer diagnosis was 1.645, with a sensitivity of 82.0% and a specificity of 80.9%.MiR-101 is decreased in bladder cancer patients, and shows negative association with aggressive clinical characteristics. MiR-101 may serve as a bio-marker in diagnosing bladder cancer.

Qian Z, Yang J, Liu H, et al.
The miR-1204 regulates apoptosis in NSCLC cells by targeting DEK.
Folia Histochem Cytobiol. 2019; 57(2):64-73 [PubMed] Related Publications
INTRODUCTION: This study endeavors to analyze the effects of miR-1204 on the expression of DEK oncogene in non-small cell lung cancer (NSCLC) cell lines and to study the molecular mechanisms of these effects.
MATERIAL AND METHODS: The miR-1204 mimics and inhibitors were transfected into the (A549 and SPC) NSCLC cells. Then the mRNA levels, cell viability, apoptosis rate, morphology and caspase activity were determined. The expression of apoptosis-related proteins Bcl-2 and Bax was also analyzed.
RESULTS: In NSCLC cell lines (A549 and SPC), DEK mRNA levels were down-regulated in miR-1204 overex-pression group. In miR-1204 inhibition group, the expression of DEK mRNA showed an opposite trend. The overexpression of miR-1204 increases the apoptosis rate in NSCLC cells. The Bcl-2 levels in the miR-1204 over-expression group were decreased, while the Bax level was increased. In the miR-1204 inhibition group, expression of Bcl-2 and Bax showed opposite trends. Cell staining revealed cell's morphological changes; the apoptosis in the miR-1204 overexpression group revealed significant morphological features, such as brighter nuclei and nu-clear condensation. Results indicated a typical characteristic of apoptosis in the miR-1204 overexpression group. Caspase-9 and Caspase-3 were involved in the apoptosis pathway, which was mediated by miR-1204 and DEK.
CONCLUSIONS: The miR-1204 induces apoptosis of NSCLC cells by inhibiting the expression of DEK. The mech-anism of apoptosis involves down-regulation of Bcl-2 and up-regulation of Bax expression. Moreover, the apoptosis was mediated by mitochondria-related caspase 9/3 pathway.

Zhang H, Luo C, Zhang G
DNA Cell Biol. 2019; 38(8):857-864 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) has been reported to be one of the major tumors in the world. There is a study indicating that MCM3AP-AS1 is an oncogenic factor in HCC; however, the mechanism by which MCM3AP-AS1 regulates HCC remains not fully understood. Reverse Transcription-quantitative PCR and Western blot approaches were used to detect mRNA and protein levels of various genes. To examine invasion of HCC cells and lymphatic vessel formation of human dermal lymphatic endothelial cells (HDLECs), we employed transwell invasion assay and lymphatic vessel assay. Bioinformatic analysis and luciferase reporter assay were used to establish direct interactions between MCM3AP-AS1 and miR-455. Besides, The Cancer Genome Atlas analyses of HCCs were performed to determine the association of MCM3AP-AS1 and epidermal growth factor receptor (EGFR) with overall survival. MCM3AP-AS1 knockdown impaired invasion of HCC cells and lymphatic vessel formation of HDLECs. MCM3AP-AS1 directly interacted with miR-455. Furthermore, miR-455 inhibitor-transfected HepG2 cells enhanced the invasion and lymphatic vessel formation abilities. The rescue experiments indicated that EGFR was critical for MCM3AP-AS1- and miR-455-regulated invasion and lymphatic vessel formation. More interestingly, autophagy-related genes (Beclin1, LC3 II/I, and ATG7) were abnormally regulated in miR-455 mimic or inhibitor HepG2 cells. miR-455 mimic inhibited cell invasion and lymphatic vessel formation, which was evidently abrogated by ATG7 overexpression. Finally, we analyzed The Cancer Genome Atlas data sets to test the upregulated expression levels of MCM3AP-AS1 and EGFR. In addition, the results showed that low levels of both genes facilitate survival of HCC patients. In this study, we reveal a novel mechanism underlying MCM3AP-AS1-induced HCC metastasis by regulating miR-455. The conclusions provide more insights into understanding mechanism underlying HCC and help development of therapeutical approaches for treating HCC.

Gao YL, Cui Z, Liu JX, et al.
NPCMF: Nearest Profile-based Collaborative Matrix Factorization method for predicting miRNA-disease associations.
BMC Bioinformatics. 2019; 20(1):353 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Predicting meaningful miRNA-disease associations (MDAs) is costly. Therefore, an increasing number of researchers are beginning to focus on methods to predict potential MDAs. Thus, prediction methods with improved accuracy are under development. An efficient computational method is proposed to be crucial for predicting novel MDAs. For improved experimental productivity, large biological datasets are used by researchers. Although there are many effective and feasible methods to predict potential MDAs, the possibility remains that these methods are flawed.
RESULTS: A simple and effective method, known as Nearest Profile-based Collaborative Matrix Factorization (NPCMF), is proposed to identify novel MDAs. The nearest profile is introduced to our method to achieve the highest AUC value compared with other advanced methods. For some miRNAs and diseases without any association, we use the nearest neighbour information to complete the prediction.
CONCLUSIONS: To evaluate the performance of our method, five-fold cross-validation is used to calculate the AUC value. At the same time, three disease cases, gastric neoplasms, rectal neoplasms and colonic neoplasms, are used to predict novel MDAs on a gold-standard dataset. We predict the vast majority of known MDAs and some novel MDAs. Finally, the prediction accuracy of our method is determined to be better than that of other existing methods. Thus, the proposed prediction model can obtain reliable experimental results.

Zhu Y, Wang J, Wang F, et al.
Differential MicroRNA Expression Profiles as Potential Biomarkers for Pancreatic Ductal Adenocarcinoma.
Biochemistry (Mosc). 2019; 84(5):575-582 [PubMed] Related Publications
Pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge due to its poor prognosis. Therefore, the early diagnosis of PDAC is extremely important for achieving a cure. MicroRNAs (miRNAs) could serve as a potential biomarker for the early detection and prognosis of PDAC. In this work we analyzed plasma samples from healthy persons and PDAC patients to assess differential miRNA expression profiles by next generation sequencing technology and bioinformatics analysis. In this way, 165 mature miRNAs were found to be significantly deregulated in the patient group, of which 75 and 90 mature miRNAs were up- and down-regulated compared with healthy individuals, respectively. Furthermore, 1029 novel miRNAs were identified. In conclusion, plasma miRNA expression profiles are different between healthy individuals and patients with PDAC. These data provide a possibility for use of miRNA as diagnostic and prognostic biomarkers of PDAC.

Xiang D, Tian B, Yang T, Li Z
miR-222 expression is correlated with the ATA risk stratifications in papillary thyroid carcinomas.
Medicine (Baltimore). 2019; 98(25):e16050 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: miR-222 is one of the most consistently overexpressed miRNAs in papillary thyroid carcinoma (PTC). Previous studies demonstrated that miR-222 overexpression conferred high-risk features in PTC patients, suggesting its value in risk-stratification. However, studies in term of miR-222's utility on stratifying PTCs are lacking.
METHODS: One hundred patients including 10 with multinodular goiter and 90 with PTC were enrolled. Formalin-fixed paraffin-embedded samples were exploited for miR-222 quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Correlations between miR-222 expression and different clinicopathological features, Tumor-node-metastasis (TNM) staging and ATA risk level were analyzed.
RESULTS: miR-222 expression of the PTC group was significantly higher than that of the goiter group (P < .001). Furthermore, miR-222 expression was significantly higher in PTCs with advanced features like larger tumor, capsular invasion, vascular invasion and lymph nodes metastasis. The majority of patients (61%) were in stage I group (similar to ATA low-risk) by TNM staging system. As to the ATA system, the majority (73%) were in intermediate-risk group (similar to TNM stage II and III roughly). Contrary to previous report, here we found that miR-222 expression was correlated with the ATA risk level (P < .001), but not with the TNM staging (P = .122).
CONCLUSION: In the present study, we demonstrated that miR-222 overexpression was correlated with advanced features like capsular invasion, vascular invasion, larger tumor size and lymph node metastasis in PTCs. Most importantly, miR-222 expression was correlated with ATA risk levels, suggesting its potential value in PTC risk-stratification.

Blanca A, Sanchez-Gonzalez A, Requena MJ, et al.
Expression of miR-100 and miR-138 as prognostic biomarkers in non-muscle-invasive bladder cancer.
APMIS. 2019; 127(8):545-553 [PubMed] Related Publications
microRNA alterations are involved in bladder cancer tumorigenesis. The aim of the current study was to evaluate the potential role of miR-100 and miR-138 as prognostic biomarkers in Ta/T1 non-muscle-invasive bladder cancer (NMIBC). We assessed a quantitative RT-PCR analysis of miR-100 and miR-138 in 50 bladder tumor samples (stage Ta/T1) and four healthy adjacent tissues. Western blot analysis was used to measure protein expression of FGFR3 and cyclin D3 in order to know whether these targets can be regulated by miR-100 and miR-138, respectively. The statistical analysis included non-parametric tests (Mann-Whitney U and Kruskal-Wallis) and univariate survival analysis by Kaplan-Meier method and the log-rank test. Low expression of miR-138 characterized recurrent tumors (p = 0.043), and higher expression levels were associated with longer recurrence-free survival (p = 0.012). However, low miR-100 expression correlated with longer progression-free survival (marginal significance; p = 0.053) and cancer-specific overall survival (p = 0.006). Additionally, higher levels of miR-100 were associated with negative FGFR3 protein expression (p = 0.032) and higher levels of miR-138 were associated with positive cyclin D3 protein expression (p = 0.037). Our results support miR-138 and miR-100 as prognostic biomarkers in patients with NMIBC.

Vieira IA, Recamonde-Mendoza M, da Silva VL, et al.
A comprehensive analysis of core polyadenylation sequences and regulation by microRNAs in a set of cancer predisposition genes.
Gene. 2019; 712:143943 [PubMed] Related Publications
Two core polyadenylation elements (CPE) located in the 3' untranslated region of eukaryotic pre-mRNAs play an essential role in their processing: the polyadenylation signal (PAS) AAUAAA and the cleavage site (CS), preferentially a CA dinucleotide. Herein, we characterized PAS and CS sequences in a set of cancer predisposition genes (CPGs) and performed an in silico investigation of microRNAs (miRNAs) regulation to identify potential tumor-suppressive and oncogenic miRNAs. NCBI and alternative polyadenylation databases were queried to characterize CPE sequences in 117 CPGs, including 81 and 17 known tumor suppressor genes and oncogenes, respectively. miRNA-mediated regulation analysis was performed using predicted and validated data sources. Based on NCBI analyses, we did not find an established PAS in 21 CPGs, and verified that the majority of PAS already described (74.4%) had the canonical sequence AAUAAA. Interestingly, "AA" dinucleotide was the most common CS (37.5%) associated with this set of genes. Approximately 90% of CPGs exhibited evidence of alternative polyadenylation (more than one functional PAS). Finally, the mir-192 family was significantly overrepresented as regulator of tumor suppressor genes (P < 0.01), which suggests a potential oncogenic function. Overall, this study provides a landscape of CPE in CPGs, which might be useful in development of future molecular analyses covering these frequently neglected regulatory sequences.

Chen S, Yang C, Sun C, et al.
miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG.
DNA Cell Biol. 2019; 38(8):865-873 [PubMed] Related Publications
Accumulating evidence has suggested that microRNAs play important roles in the development of hepatocellular carcinoma (HCC) and are involved in drug resistance. miR-21-5p was overexpressed in a variety of cancers and promoted the tumorigenesis; however, the function of miR-21-5p in HCC still remains unknown. In this study, our results showed that miR-21-5p was highly expressed in HCC tissues and cell lines. Notably, the level of miR-21-5p was relatively higher in cisplatin (DDP)-resistant HCC patients. Overexpression of miR-21-5p attenuated the inhibitory effect of DDP on the proliferation and apoptosis of HCC cells. Mechanistically, the luciferase report assay-identified FAS ligand (FASLG) was a direct target of miR-21-5p. Overexpression of miR-21-5p decreased both the mRNA and protein levels of FASLG in HCC cells. FASLG was downregulated in HCC tissues and was significantly negatively correlated with the expression of miR-21-5p. Restoring the expression of FASLG upregulated the chemosensitivity of HCC cells expressing miR-21-5p. In conclusion, our results demonstrated that miR-21-5p targeted FASLG and suppressed the sensitivity of HCC cells to DDP treatment.

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