The miRNA miR-139-5p is a regulator of metastatic pathways in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Cloonan Nicole
PROVIDER: S-ECPF-GEOD-40411 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGF?, Wnt, Rho, and MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate. To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.
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Project description:Whole transcriptome Identification of direct targets of miR-139-5p using biotinylated pull-downs found that this miRNA has roles in breast cancer invasion and migration. MCF7 cells were transfected with biotinylated miR-139-5p. The miRNAs and target mRNA were pulled down with streptavidin and compared to the input control.
2013-12-01 | E-GEOD-40411 | biostudies-arrayexpress
Project description:Whole transcriptome Identification of direct targets of miR-139-5p using biotinylated pull-downs found that this miRNA has roles in breast cancer invasion and migration.
2013-12-01 | GSE40411 | GEO
Project description:Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.
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Project description:MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein-coding genes by partially binding to specific target sites of mRNAs. miRNAs perform important functions in complicated cellular biological processes and their abnormal expression is involved in various disorders, including cancer. Among the miRNAs, differential expression of miR-139-5p serves a significant role in tumorigenesis, metastasis and recurrence, thus suggesting that it may potentially be used as a promising biomarker for cancer diagnosis, prognosis and therapy. miR-139-5p is expected to serve as a biomarker to eventually be implemented in a clinical setting. In the present review, we focus on the importance of miR-139-5p in cancer, summarize the association between miR-139-5p expression level and diagnosis and prognosis, and discuss the potential therapeutic implications for the future.
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Project description:BackgroundEndometrial cancer (EC) is the fourth most common malignancy of the female genital tract worldwide. MicroRNAs are important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Several study's show that miR-139-5p is involved in the tumorigenesis and metastasis of various cancers. However, its expression and potential biologic role in endometrial cancer remain to be determined. This study aimed to investigate the miR-139-5p expression and to analyze its function and underlying molecular mechanism in endometrial cancer.MethodsExpression of miR-139-5p was measured using qRT-PCR. The expression of HOXA10 was detected by Immunofluorescence staining in endometrial cancer tissues and adjacent normal tissues. CCK-8 and colony formation assays were used to assess the effect of miR-139-5p on ECC1 and Ishikawa cell line proliferation. Transwell migration assay was used to study the effect of miR-139-5p on EC cell migration. Luciferase reporter assay and western blot were used to confirm targeting of HOXA10 by miR-139-5p.ResultWe demonstrated that miR-139-5p was down-regulated in human endometrial cancer compared to their matched adjacent non-tumor tissues. Overexpressed miR-139-5p significantly inhibited endometrial cancer cell viability and migration. Computational algorithm in combination with dual luciferase reporter assays identified HOXA10 as the target of miR-139-5p. HOXA10 expression was downregulated in endometrial cancer cells after miR-139-5p overexpression. The expression level of HOXA10 was significantly increased in endometrial cancer tissues, which was inversely correlated with miR-139-5p expression in clinical endometrial cancer tissues.ConclusionThese findings indicate that miR-139-5p targets the HOXA10 transcript and suppresses endometrial cancer cell growth and migration, suggesting that miR-139-5p acts as a tumor suppressive role in human endometrial cancer pathogenesis.
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Project description:To identify differentially expressed genes by miRNAs transfection in human cancer, lung adenocarcinoma cells were subjected to agilent whole genome microarrays
2023-10-11 | GSE242241 | GEO
Project description:PurposeRadioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy.MethodsWe analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization.ResultsThe finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function.ConclusionsOur study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC.
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Project description:To evaluate gene expression alteration following miR-139-5p transfection in glioma cells. We find a significant downregulation of two transcriptional factors, E2F3 and HoxA9. Total RNA were extracted from U87, LN229 and U251 glioma cells transfected with miR-139-5p or miRNA negative control.
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Project description:We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p < 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p < 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial-mesenchymal transition. Involvement of the miR-139-3p passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC.
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