Dataset Information

MiR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro.

ABSTRACT: In cancer cells, microRNAs (miRNAs) are often aberrantly expressed resulting in impaired mRNA translation. In this study we show that miR-193b and miR-30c-1* inhibit, whereas miR-576-5p accelerates invasion of various human melanoma cell lines. Using Boyden chamber invasion assays the effect of selected miRNAs on the invasive capacity of various human melanoma cell lines was analyzed. Upon gene expression profiling performed on transfected A375 cells, CTGF, THBS1, STMN1, BCL9, RAC1 and MCL1 were identified as potential targets. For target validation, qPCR, Western blot analyses or luciferase reporter assays were applied. This study reveals opposed effects of miR-193b / miR-30c-1* and miR-576-5p, respectively, on melanoma cell invasion and on expression of BCL9 and MCL1, possibly accounting for the contrasting invasive phenotypes observed in A375 cells transfected with these miRNAs. The miRNAs studied and their targets identified fit well into a model proposed by us explaining the regulation of invasion associated genes and the observed opposed phenotypes as a result of networked direct and indirect miRNA / target interactions. The results of this study suggest miR-193b and miR-30c-1* as tumor-suppressive miRNAs, whereas miR-576-5p appears as potential tumor-promoting oncomiR. Thus, miR-193b and miR-30c-1* mimics as well as antagomiRs directed against miR-576-5p might become useful tools in future therapy approaches against advanced melanoma.

SUBMITTER: Kordaß T

PROVIDER: S-EPMC6126698 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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miR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro.

Kordaß Theresa T Weber Claudia E M CEM Eisel David D Pane Antonino A AA Osen Wolfram W Eichmüller Stefan B SB

Oncotarget 20180821 65

In cancer cells, microRNAs (miRNAs) are often aberrantly expressed resulting in impaired mRNA translation. In this study we show that miR-193b and miR-30c-1* inhibit, whereas miR-576-5p accelerates invasion of various human melanoma cell lines. Using Boyden chamber invasion assays the effect of selected miRNAs on the invasive capacity of various human melanoma cell lines was analyzed. Upon gene expression profiling performed on transfected A375 cells, CTGF, THBS1, STMN1, BCL9, RAC1 an ...[more]

PMID: 30197759

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Project description:Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinformatically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa.

Project description:Purpose:Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. Patients and Methods:MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. Results:The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ?3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and ?-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. Conclusion:Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.

Dataset Information

MiR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell invasion in vitro.

Publications

miR-193b and miR-30c-1<sup>*</sup> inhibit, whereas miR-576-5p enhances melanoma cell invasion <i>in vitro</i>.

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