Research IndicatorsGraph generated 31 August 2019 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex
Specific Cancers (13)
Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.
|Tissue||Target Gene(s)||Regulator(s)||MIR10A Function in Cancer||Effect|
-Nucleophosmin1 mutated acute myeloid leukaemia (1)
-acute myeloid leukemia (1)
-chronic myeloid leukemia (1)
|inhibit cell death (1)|
increase clonogenic capacity (1)
inhibit cell growth (1)
-pancreatic cancer (2)
|RARA (1)||promote cell invasion (2)|
promote metastasis (1)
|promote cell differentiation (2)|
-cervical cancer (1)
|DDX11 (1)||promote colony formation (1)|
promote cell migration (1)
promote cell invasion (1)
-breast cancer (1)
-glioblastoma stem cells (1)
Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.
miRBase, University of Manchester
Annotated database entry including the location and sequence of the mature miRNA sequence.
miRCancer, East Carolina University
Search miRCancer for miR-10a associations with cancer and associated genes.
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: MIR10A (cancer-related)
Dong D, Mu Z, Wei N, et al.Long non-coding RNA ZFAS1 promotes proliferation and metastasis of clear cell renal cell carcinoma via targeting miR-10a/SKA1 pathway.
Biomed Pharmacother. 2019; 111:917-925 [PubMed
] Related Publications
BACKGROUND: LncRNA ZFAS1 (ZNFX1 antisense RNA1) plays key roles in the occurrence and progression of various cancers, including colorectal cancer, glioma, lung cancer, gastric cancer, and so on. To date, relatively little is known about its potential role in development and/or progression of clear cell renal cell carcinoma (ccRCC).
METHODS: Expression level of ZFAS1 and miR-10a in 60 ccRCC and 20 adjacent non-tumor tissues were determined by using qRT-PCR. The effect of knockdown of ZFAS1 on cell proliferation, migration and invasion were measured by CCK-8 assay, transwell migration and invasion assay, respectively. The correlation of ZFAS1 and miR-10a was analyzed by bioinformatics DIANA TOOLS. Protein and mRNA expression of spindle and kinetochore-associated protein 1(SKA1) were determined by western blot and qRT-PCR analysis, respectively. Interactions between ZFAS1 and miR-10a were verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay, and interactions between miR-10a and SKA1 was verified by a luciferase reporter assay.
RESULTS: We observed that high-level expression of ZFAS1 is positively correlated with poor prognosis and shorter overall survival (OS) in patients with ccRCC. Knockdown of ZFAS1 significantly suppressed proliferation, migration and invasion of ccRCC cells. Furthermore, miR-10a was identified as a target of ZFAS1. Silencing miR-10a could attenuate the ability of ZFAS1 in promoting proliferation and metastasis of ccRCC. Subsequently, our studies validated that SKA1, as a key downstream target protein for miR-10a, is responsible for the biological role of ZFAS1. ZFAS1 positively regulated SKA1 expression via sponging miR-10a.
CONCLUSIONS: Taken together, our findings suggest that ZFAS1 promotes growth and metastasis of ccRCC via targeting miR-10a/SKA1 pathway, which may represent a novel therapeutic target or biomarker for ccRCC.
Valiollahi E, Ribera JM, Genescà E, Behravan JGenome-wide identification of microRNA signatures associated with stem/progenitor cells in Philadelphia chromosome-positive acute lymphoblastic leukemia.
Mol Biol Rep. 2019; 46(1):1295-1306 [PubMed
] Related Publications
Acute lymphoblastic leukemia (ALL) is a malignant transformation with uncontrolled proliferation of lymphoid precursor cells within bone marrow including a dismal prognosis after relapse. Survival of a population of quiescent leukemia stem cells (LSCs, also termed leukemia-initiating cells (LICs)) after treatment is one of the relapse reasons in Ph
Wang Z, Lv J, Zou X, et al.A three plasma microRNA signature for papillary thyroid carcinoma diagnosis in Chinese patients.
Gene. 2019; 693:37-45 [PubMed
] Related Publications
Whether plasma miRNAs could be used as novel non-invasive biomarkers in diagnosing papillary thyroid carcinoma (PTC) remains unknown. In this study, we designed a four-phase study to identify differentially expressed plasma miRNAs in Chinese PTC patients. Exiqon panel was initially utilized to conduct plasma miRNA profile (3 PTC pools VS. 1 healthy control (HC) pool; each 10 samples were pooled as 1 sample). The dysregulated miRNAs were then analyzed in the training (30 PTC VS. 30 HCs), testing (57 PTC VS. 54 HCs) and external validation phases (33 PTC VS. 30HCs). The identified miRNAs were further affirmed in benign nodules (2 nodular goiter (NG) pool VS. 1 HC pool). We also verified the expression of identified miRNAs in 17 matched malignant and normal tissue samples, NG plasma samples (29 PTC VS. 29 NG) and plasma exosomes (25 PTC VS. 25 HCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the identified miRNAs. As a result, the screening phase demonstrated 30 dysregulated plasma miRNAs in PTC patients compared with HCs. After multiphase experiment processes, miR-346, miR-10a-5p and miR-34a-5p were found significantly elevated in PTC plasma samples relative to HCs. The areas under the ROC curve (AUC) of the three-miRNA panel for the training, testing and validation phases were 0.926, 0.811 and 0.816, separately. The panel could also differentiate PTC from NG with the AUC of 0.877. MiR-346 and miR-34a-5p but not miR-10a-5p were up-regulated in PTC tissues. And the three miRNAs showed consistently up-regulation in PTC plasma exosomes. In conclusion, our study established a three-miRNA panel in plasma with considerable clinical value in discriminating PTC from HC or NG.
Despite the rapidly identified numbers of lncRNA in humans, exploration of the molecular mechanisms of lncRNA is lagging, because the molecular mechanisms of lncRNA can be various and complex in different conditions. In this study, we found a new molecular mechanism for a versatile molecule, MIR22HG. MIR22HG is an lncRNA that contributes to the initiation and progression of many human cancers, including hepatocellular carcinoma (HCC). We report that MIR22HG was downregulated in 120 HCC samples compared with adjacent nontumor liver tissues. More interestingly, decreased expression of MIR22HG in HCC could predict poor prognosis of HCC patients. Knockdown of MIR22HG promoted the growth, migration and invasion of HCC cells. In exploring the molecular mechanism of MIR22HG, we found that MIR22HG functioned as a tumor suppressor in hepatocellular carcinomas, in part through serving as a competing endogenous RNA to modulate the miRNA-10a-5p level. Moreover, NCOR2 was verified to act as the downstream target gene of MIR22HG/miR-10a-5p. In addition, the MIR22HG/miRNA-10a-5p/NCOR2 axis inhibited the activation of the Wnt/β-catenin pathway. Together, our results demonstrated that MIR22HG inhibited HCC progression in part through the miR-10a-5p/NCOR2 signaling axis and might act as a new prognostic biomarker for HCC patients.
BACKGROUND: Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes. Although abnormalities in cytokine signaling are common in MPN, the pathophysiology of atypical MPN still remains elusive. Since deregulation of microRNAs is involved in the biology of various cancers, we studied the miRNome of aMPN patients.
METHODS: MiRNome and mutations in epigenetic regulator genes ASXL1, TET2, DNMT3A, EZH2 and IDH1/2 were explored in aMPN patients. Epigenetic regulation of miR-10a and HOXB4 expression was investigated by treating hematopoietic cell lines with 5-aza-2'deoxycytidine, valproic acid and retinoic acid. Functional effects of miR-10a overexpression on cell proliferation, differentiation and self-renewal were studied by transducing CD34
RESULTS: MiR-10a was identified as the most significantly up-regulated microRNA in aMPN. MiR-10a expression correlated with that of HOXB4, sitting in the same genomic locus. The transcription of these two genes was increased by DNA demethylation and histone acetylation, both necessary for optimal expression induction by retinoic acid. Moreover, miR-10a and HOXB4 overexpression seemed associated with DNMT3A mutation in hematological malignancies. However, overexpression of miR-10a had no effect on proliferation, differentiation or self-renewal of normal hematopoietic progenitors.
CONCLUSIONS: MiR-10a and HOXB4 are overexpressed in aMPN. This overexpression seems to be the result of abnormalities in epigenetic regulation mechanisms. Our data suggest that miR-10a could represent a simple marker of transcription at this genomic locus including HOXB4, widely recognized as involved in stem cell expansion.
BACKGROUND: Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their 'cell of origin'.
METHOD: Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls.
RESULTS: Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes.
CONCLUSION: The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients' prognosis or response to therapy.
Browne BM, Stensland KD, Patel CK, et al.MicroRNA Expression Profiles in Upper Tract Urothelial Carcinoma Differentiate Tumor Grade, Stage, and Survival: Implications for Clinical Decision-Making.
Urology. 2019; 123:93-100 [PubMed
] Related Publications
OBJECTIVE: To evaluate microRNA (miRNA) biomarkers for upper tract urothelial carcinoma (UTUC) to improve risk stratification.
METHODS: miRNA was isolated from 157 radical nephroureterectomy specimens from 2 institutions. The relative expression of miRNA was examined for high grade vs low grade tumors as well as muscle invasive vs nonmuscle invasive tumors. Recurrence free survival (RFS) and overall survival (OS) were also stratified using relative expression of specific miRNA.
RESULTS: The optimized model to identify high grade UTUC included miR-29b-2-5p, miR-18a-5p, miR-223-3p, and miR-199a-5p, generating a sensitivity of 83%, specificity of 85%, and generated a receiver operating characteristic (ROC) curve with area-under-the-curve of 0.86. Similarly, the model classifier for predicting ≥pT2 disease incorporated miR-10b-5p, miR-26a-5p-5p, miR-31-5p, and miR-146b-5p, producing a sensitivity of 64%, specificity of 96%, and area-under-the-curve of 0.90. RFS was best reflected by a combination of miR-10a-5p, miR-30c-5p, and miR-10b-5p, while OS was best predicted by miR-10a-5p, miR-199a-5p, miR-30c-5p, and miR-10b-5p.
CONCLUSION: High-grade vs low-grade as well as muscle invasive vs nonmuscle invasive UTUC can be reliable distinguished with unique miRNA signatures. Furthermore, differential expression of UTUC miRNA produces robust classifiers for predicting RFS and OS that may help identify patients who would most benefit from adjuvant therapies.
Grolmusz VK, Kövesdi A, Borks K, et al.Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms
Eur J Endocrinol. 2018; 179(4):219-228 [PubMed
] Related Publications
Objective: Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas; however, their prognosis differs significantly upon their proliferative state, which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs.
Methods: MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the reanalysis were confirmed by qRT-PCR analysis of five miRNAs on an independent validation cohort of 63 primary PanNEN samples. Cox proportional hazards survival regression models were fit for both univariate and multivariate analysis to determine the miRNAs’ effect on progression-free and overall survival.
Results: Nineteen miRNAs displayed differential expression between tumor grades. The altered expression of three out of five chosen miRNAs was successfully validated; hsa-miR-21, hsa-miR-10a and hsa-miR-106b were upregulated in more proliferative PanNENs compared to Grade 1 tumors. In univariate analysis, higher expression of tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b of primary PanNENs predicted worse progression-free and overall survival; however, multivariate analysis only confirmed the expression of hsa-miR-21 as an independent prognostic factor.
Conclusions: The expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR-21 has prognostic relevance regarding progression-free and overall survival in patients with PanNENs.
Xu H, Li Y, Han B, et al.Anti-breast-Cancer Activity Exerted by β-Sitosterol-d-glucoside from Sweet Potato via Upregulation of MicroRNA-10a and via the PI3K-Akt Signaling Pathway.
J Agric Food Chem. 2018; 66(37):9704-9718 [PubMed
] Related Publications
Breast cancer (BC) is a prominent source of cancer mortality in women throughout the world. β-Sitosterol-d-glucoside (β-SDG), a newly isolated phytosterol from sweet potato, possibly displays potent anticancer activity. However, the probable anticancer mechanisms involved are still unclear. This study sought to study how β-SDG from sweet potato affects two BC cell lines (MCF7 and MDA-MB-231) and nude mice bearing MCF7-induced tumors. In addition, we assessed how β-SDG affects tumor suppressor miR-10a and PI3K-Akt signaling in BC cells. Cell viability and proliferation were determined via MTT and colony-formation assays, and apoptosis was quantified by Hoechst staining and flow cytometry. In addition, miR-10a expression and apoptosis-related protein levels were measured. Our study indicated that β-SDG exhibited cytotoxic activities on MCF7 and MDA-MB-231 cells via inducing apoptosis and activating caspase proteases in these cells. Furthermore, the experimental results in nude mice bearing MCF7-induced tumors demonstrated that oral β-SDG administration at medium (60 mg/kg) or high (120 mg/kg) doses was sufficient to substantially impair the growth of tumors and to decrease the levels of CEA, CA125, and CA153 by 64.71, 74.64, and 85.32%, respectively, relative to those of the controls ( P < 0.01). β-SDG was further found to regulate the expression of PI3K, p-Akt, Bcl-2-family members, and other factors involved in the PI3K-Akt-mediated mitochondrial signaling pathway via the tumor suppressor miR-10a. These findings indicated that β-SDG suppresses tumor growth by upregulating miR-10a expression and inactivating the PI3K-Akt signaling pathway. Furthermore, β-SDG could be developed as a potential therapeutic agent against MCF7-cell-related BC.
Kim C, Go EJ, Kim ARecurrence prediction using microRNA expression in hormone receptor positive breast cancer during tamoxifen treatment.
Biomarkers. 2018; 23(8):804-811 [PubMed
] Related Publications
PURPOSE: To identify miRNAs associated with distant recurrence during tamoxifen treatment and build a recurrence prediction model.
MATERIALS AND METHODS: We measured the expression of five miRNAs (miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222). A total of 176 tumour tissues from 176 patients who had hormone receptor positive breast cancer with tamoxifen treatment were used to measure miRNA expression using quantitative real-time PCR (qRT-PCR).
RESULTS: The five miRNAs were all up-regulated in distant recurrence cases within 5 years after surgery and during tamoxifen treatment. Kaplan-Meier survival analyses based on expression cut-offs determined by receiver characteristics curves (ROC) showed that high expression of miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222 were significantly (log-rank p-value =0.006, p-value <0.0001, p-value <0.0001, p-value <0.0001 and p-value <0.0001, respectively) associated with short relapse-free time. Our results were used to build a combined 3 miRNAs expression model. It could be used to categorize high-risk subset of patients with short relapse-free survival (AUC =0.891, p-value <0.0001).
CONCLUSIONS: Distant recurrence during tamoxifen treatment of hormone positive breast cancer might be affected by tamoxifen resistance related miRNAs. Such distant recurrence can be predicted using miRNA measurement.
AIM: To determine a panel of serum microRNAs (miRNAs) that could be used as novel biomarkers for diagnosis of hepatocellular carcinoma (HCC).
METHODS: We initially screened 9 out of 754 serum miRNAs by TaqMan Low Density Array in two pooled samples respectively from 35 HCC and 35 normal controls, and then validated individually by RT-qPCR in another 114 patients and 114 controls arranged in two phases. The changes of the selected miRNAs after operation and their prognostic value were examined.
RESULTS: miR-375, miR-10a, miR-122 and miR-423 were found to be significantly higher in HCC than in controls (
CONCLUSION: The four serum miRNAs (miR-375, miR-10a, miR-122 and miR-423) could potentially serve as novel biomarkers for the diagnostic and prognostic of HCC.
BACKGROUND: Invasive cervical cancer (ICC) is caused by high-risk human papillomavirus types (HR-HPVs) and is usually preceded by a long phase of intraepithelial neoplasia (CIN). Before invasion, (epi) genetic changes, potentially applicable as molecular markers within cervical screening, occur in HPV host cells. Epigenetic alterations, such as dysregulation of microRNA (miRNA) expression, are frequently observed in ICC. The mechanisms and role of miRNA dysregulation in cervical carcinogenesis are still largely unknown.
METHODS: We provide an overview of the studies investigating miRNA expression in relation to ICC progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched through Pubmed database all articles between January 2010 and December 2017.
RESULTS: From the 24 studies retrieved, miR-29a and miR-21 are the most frequently down- and up-regulated in ICC progression, respectively. Microarray-based studies show a small overlap, with miR-10a, miR-20b, miR-9, miR-16 and miR-106 found repeatedly dysregulated. miR-34a, miR-125 and miR-375 were also found dysregulated in cervical exfoliated cells in relation to cancer progression.
CONCLUSIONS: The pivotal role of miRNAs in ICC progression and initial development is becoming more and more relevant. Available studies are essentially based on convenience material, entailing possible selection bias, and frequently of small size: all these points still represent a limitation to a wide comprehension of miRNAs relevant for ICC. The targeted approach instead of a genome-wide investigation still precludes the identification of all the relevant miRNAs in the process. The implementation of deep sequencing on large scale population-based studies will help to discover and validate the relation between altered miRNA expression and CC progression for the identification of biomarkers. Optimally, once explored on a miRNome scale, small specific miRNA signatures maybe used in the context of screening.
Zhu HR, Huang RZ, Yu XN, et al.Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma.
Tohoku J Exp Med. 2018; 245(2):89-98 [PubMed
] Related Publications
Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.
Guo X, Qiu W, Liu Q, et al.Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a/Rora and miR-21/Pten Pathways.
Oncogene. 2018; 37(31):4239-4259 [PubMed
] Related Publications
While immunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) have been well documented in glioma patients, the mechanisms of MDSC development and activation have not been clearly defined. Here, we elucidated a role for glioma-derived exosomes (GDEs) in potentiating an MDSC pathway. We isolated normoxia-stimulated and hypoxia-stimulated GDEs and studied their MDSC induction abilities in vivo and in vitro. Analyses of spleen and bone marrow MDSC proportions (flow cytometry) and reactive oxygen species (ROS), arginase activity, nitric oxide (NO), T-cell proliferation and immunosuppressive cytokine (IL-10 and TGF-β, ELISA) levels were used to assess MDSC expansion and functional capacity. We also performed microRNA (miRNA) sequencing analysis of two types of GDEs to find miRNAs that potentially mediate the development and activation of MDSCs. GDE miRNA intracellular signaling in MDSCs was also studied. Hypoxia promoted the secretion of GDEs, and mouse MDSCs could uptake GDEs. Hypoxia-stimulated GDEs had a stronger ability to induce MDSCs than N-GDEs. The hypoxia-inducible expression of miR-10a and miR-21 in GDEs mediated GDE-induced MDSC expansion and activation by targeting RAR-related orphan receptor alpha (RORA) and phosphatase and tensin homolog (PTEN). Mice inoculated with miR-10a or miR-21 knockout glioma cells generated fewer MDSCs than those inoculated with normal glioma cells. These data elucidated a mechanism by which glioma cells influence the differentiation and activation of MDSCs via exosomes and demonstrated how local glioma hypoxia affects the entirety of tumor immune environments.
Kong F, Li L, Wang G, et al.VDR signaling inhibits cancer-associated-fibroblasts' release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells.
Gut. 2019; 68(5):950-951 [PubMed
] Related Publications
BACKGROUND: By regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear.
METHODS: The effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated.
RESULTS: We found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC.
CONCLUSION: Together, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC.
Shang C, Tang W, Pan C, et al.Long non-coding RNA TUSC7 inhibits temozolomide resistance by targeting miR-10a in glioblastoma.
Cancer Chemother Pharmacol. 2018; 81(4):671-678 [PubMed
] Related Publications
PURPOSE: Human glioblastoma multiforme (GBM) is the most malignant intracranial primary cancer and is associated with high mortality and poor prognosis. This study aimed to investigate the regulatory effects and mechanism of tumor suppressor candidate 7 (TUSC7) gene to malignant proliferation and chemotherapy resistance to temozolomide (TMZ) in glioma cells.
METHODS: The expression of TUSC7 was detected by quantitative real-time PCR. CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry were used to detect cell cycle and cell apoptosis. The expression of MDR1 protein was examined by western blot. RNA pull-down assay was applied to confirm the specific combination between TUSC7 and miR-10a.
RESULTS: In the present study, we detected low expression of TUSC7 in GBM cells and tissues resistant to TMZ. Upregulation of TUSC7 suppressed both TMZ resistance and expression of multidrug resistance protein 1 (MDR1) in U87TR cells. TUSC7 acted by directly targeting and silencing expression of miR-10a gene, and miR-10a mediated TUSC7-induced inhibition on TMZ resistance in U87TR cells.
CONCLUSIONS: These findings suggest a negative correlation between TUSC7 expression and TMZ resistance and provide a mechanism and rationale for targeting TUSC7 in the treatment of GBM.
Lundberg IV, Wikberg ML, Ljuslinder I, et al.MicroRNA Expression in
Anticancer Res. 2018; 38(2):677-683 [PubMed
] Related Publications
BACKGROUND/AIM: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS- and BRAF-mutated CRCs.
MATERIALS AND METHODS: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.
RESULTS: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.
CONCLUSION: Our results suggest that KRAS- and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS- and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.
Zhang TJ, Guo H, Zhou JD, et al.Bone marrow miR-10a overexpression is associated with genetic events but not affects clinical outcome in acute myeloid leukemia.
Pathol Res Pract. 2018; 214(1):169-173 [PubMed
] Related Publications
BACKGROUND: Accumulating studies have linked the disruptions of microRNA-10 (miR-10) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML.
METHODS: BM miR-10 expression was examined by real-time quantitative PCR in BM mononuclear cells in 115 de novo AML patients and 45 controls.
RESULTS: BM miR-10 (miR-10a/b) expression was significantly up-regulated in AML patients, and was positively correlated with each other. Overexpression of miR-10a was associated with lower percentage of BM blasts, whereas miR-10b overexpression tended to correlate with higher percentage of BM blasts. Importantly, miR-10a overexpression was significantly associated with FAB-M3/t(15;17) subtypes and NPM1 mutation, meanwhile, overexpression of miR-10b was correlated with NPM1 and DNMT3A mutations. However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation.
CONCLUSIONS: BM miR-10 overexpression is associated with genetic events but not affects clinical outcome in AML.
IL23/Th17 axis acts as an inflammatory pathway in gastric carcinogenesis. MicroRNA- (miRNA-) binding site single-nucleotide polymorphisms (SNPs) of inflammatory genes may alter gastric cancer (GC) susceptibility. In this study, four miRNA binding site SNPs (rs3748067 of
Ashmawy AM, Elgeshy KM, Abdel Salam ET, et al.Crosstalk between liver-related microRNAs and Wnt/β-catenin pathway in hepatocellular carcinoma patients.
Arab J Gastroenterol. 2017; 18(3):144-150 [PubMed
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BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/β-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/β-catenin signaling proteins and microRNAs expression in HCC patients.
PATIENTS AND METHODS: Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a- miR-106b- miR-99a- miR-148a- miR-125b- miR-30e- miR-183- miR-155- miR-199a- miR-199a3p- miR-24- miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/β-catenin pathway (β-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed.
RESULTS: Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p<0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/β-catenin pathway including β-catenin, APC and c-myc (p<0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection.
CONCLUSION: Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/β-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.
Cai Y, Guo H, Li HZ, et al.[MicroRNA differential expression profile in tuberous sclerosis complex cell line TSC2
Beijing Da Xue Xue Bao Yi Xue Ban. 2017; 49(4):580-584 [PubMed
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OBJECTIVE: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in the TSC1 and TSC2 genes, but the molecular events contributing to TSC are not well understood. However, little is known about the role of microRNAs in TSC. To explore the microRNA differential expression profile between tuberous sclerosis complex cell line TSC2
RESULTS: Fourteen microRNAs, including miR-18a-5p, miR-376c-3p, miR-136-5p, miR-467c-5p, miR-467b-5p, miR-5104, miR-3098-3p, miR-30a-3p, miR-302b-3p, miR-18a-3p, miR-19b-1-5p, miR-19a-5p, miR-20a-5p, miR-155-5p, were up-regulated, while twenty-six microRNAs, including miR-200b-3p, miR-450a-1-3p, miR-542-5p, miR-199b-5p, miR-10a-5p, miR-466c-5p, miR-450a-5p, miR-450b-5p, miR-542-3p, miR-351-5p, miR-322-3p, miR-199a-3p, miR-335-5p, miR-10b-5p, miR-351-3p, miR-155-3p, miR-497a-5p, miR-503-5p, miR-148a-3p, miR-1843a-5p, miR-199a-5p, miR-490-5p, miR-450a-2-3p, miR-322-5p, miR-214-3p, miR-450b-3p, were down-regulated in tuberous sclerosis complex cell line TSC2
CONCLUSION: There are differences in the expression of miRNA between the tuberous sclerosis complex cell line TSC2
Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore-associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by genome-based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR-10a-5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR-10a-5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.
Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).
Muñoz-Largacha JA, Gower AC, Sridhar P, et al.miRNA profiling of primary lung and head and neck squamous cell carcinomas: Addressing a diagnostic dilemma.
J Thorac Cardiovasc Surg. 2017; 154(2):714-727 [PubMed
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OBJECTIVE: To determine whether microRNA (miRNA) profiling of primary lung and head and neck squamous cell carcinomas could be useful to identify a specific miRNA signature that can be used to further discriminate between primary lung squamous carcinomas and metastatic lesions in patients with a history of head and neck squamous cell cancer.
METHODS: Specimens of resected primary head and neck and lung squamous cell carcinomas were obtained from formalin-fixed, paraffin-embedded blocks. Paraffin blocks were sectioned and deparaffinized, and total RNA was isolated and profiled. Quantitative polymerase chain reaction was performed to verify array results.
RESULTS: Twelve head and neck and 16 lung squamous cell carcinoma samples met quality control metrics and were included for analysis. Forty-eight miRNAs were differentially expressed (P < .05) between the 2 groups. Of these, 30 were also significantly associated (q < .25) with tumor type in 2 independent sets of primary head and neck and lung squamous carcinomas profiled by The Cancer Genome Atlas consortium, including miR-34a and miR-10a. The ratio of miR-10a and miR-10b was especially predictive of primary cancer site in all 3 data sets, with area under the (receiver operating characteristics) curve values ranging from 0.922 to 0.982. Quantitative polymerase chain reaction confirmed the association of miR-34a expression and the miR-10:miR-10b ratio with tumor type.
CONCLUSIONS: MicroRNA expression may be useful for discriminating between head and neck and lung squamous cell carcinomas, including miR-34a and the miR-10a:miR-10b ratio. This differentiation has clinical importance because it could help determine the appropriate therapeutic approach.
Kowalik CG, Palmer DA, Sullivan TB, et al.Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma.
BJU Int. 2017; 120(3):428-440 [PubMed
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OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue.
MATERIALS AND METHODS: RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses.
RESULTS: Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS.
CONCLUSION: This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.
MicroRNAs (miRNAs) have a critical role in tumorigenesis and metastasis, which are major obstacles of cancer therapy. However, the role of miRNAs in colorectal cancer (CRC) metastasis remains poorly understood. Here, we found that miRNA-10a (miR-10a) was upregulated in primary CRC tissues and cell line (SW480) derived from primary CRC compared with metastatic cancer tissues in lymph node and cell line (SW620). The differential expression of miR-10a was inversely correlated with distant metastasis and invasion depth. miR-10a promoted migration and invasion in vitro but inhibited metastasis in vivo by regulating the epithelial-to-mesenchymal transition and anoikis. Furthermore, matrix metalloproteinase 14 (MMP14) and actin gamma 1 (ACTG1) were validated as target genes of miR-10a in CRC cells. Ectopic expression of MMP14 and ACTG1 counteracted the decreased cell adhesion and anoikis resistance activities induced by miR-10a. These findings not only describe the mechanism by which miR-10a suppresses CRC metastasis but also suggest the potential prognostic and therapeutic value of miR-10a in CRC patients.
Zhang H, Lu Y, Chen E, et al.XRN2 promotes EMT and metastasis through regulating maturation of miR-10a.
Oncogene. 2017; 36(27):3925-3933 [PubMed
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MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism.
Xin F, Liu P, Ma CFA circulating serum miRNA panel as early detection biomarkers of cervical intraepithelial neoplasia.
Eur Rev Med Pharmacol Sci. 2016; 20(23):4846-4851 [PubMed
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OBJECTIVE: MicroRNAs (miRNAs) have been demonstrated to play critical roles in regulating the molecular process of tumorigenesis. Therefore, the purpose of this study was to establish a panel of serum miRNA signature for early detection of cervical intraepithelial neoplasia (CIN).
PATIENTS AND METHODS: One hundred and twenty-six patients with CIN and sixty healthy control subjects were recruited in this cohort study. Quantitative reverse transcript polymerase chain reaction (qRT-PCR) was conducted to detect the expression level of the panel of miRNA signature (miR-9, miR-10a, miR-20a and miR-196a) in the serum samples of all the participants. The association between HPV infection status and the expression levels of miRNAs was also evaluated. In addition, Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic value of the combination of these four serum miRNAs.
RESULTS: The expression levels of the four miRNAs (miR-9, miR-10a, miR-20a and miR-196a) were all significantly upregulated in the serum samples derived from the CIN patients compared with those from the healthy controls (p < 0.01). Also, HPV infection status was significantly correlated with the expression levels of miRNAs (p < 0.01). The ROC analysis showed that this four-miRNA signature showed high accuracy in discriminating CIN individuals (AUC = 0.886, p < 0.01) from healthy controls.
CONCLUSIONS: Taken together, our findings demonstrated that the panel of four serum miRNAs (miR-9, miR-10a, miR-20a and miR-196a) are useful and novel noninvasive biomarkers for early detection of CIN.
The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.