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MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis.

ABSTRACT: OBJECTIVES:MicroRNAs are powerful regulators in hepatocellular carcinoma (HCC) tumorigenesis. MicoRNA-191 (miR-191) has been reported to play an important role in HCC, However, the regulatory mechanism is still unclear. In this study, we investigated the role of miR-191 in HCC and studied its underlying mechanisms of action. MATERIALS AND METHODS:The expression of miR-191 in HCC tissues was determined by quantitative real-time PCR (qRT-PCR). The role of miR-191 in HCC cells was examined by using both in vitro and in vivo assays. Downstream targets of miR-191 were determined by qRT-PCR and Western blot analysis. Dual-luciferase assays were performed to validate the interaction between miR-191 and its targets. RESULTS:The expression of miR-191 was significantly higher in HCC patients and a higher miR-191 expression predicted poorer prognosis. Analysis of The Cancer Genome Atlas data sets suggested that miR-191 positively correlated with cell cycle progression. Gain and loss of function assays showed that miR-191 promoted cell cycle progression and proliferation. Luciferase reporter assay showed that miR-191 directly targeted the 3'-untranslated region of KLF6 mRNA. Furthermore, circular RNA has_circ_0000204 could sponge with miR-191, resulting in inactivation of miR-191. CONCLUSIONS:Our study sheds light on the novel underlying mechanism of miR-191 in HCC, which may accelerate the development of cancer therapy.

SUBMITTER: Tian F

PROVIDER: S-EPMC6797514 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis.

Tian Fang F Yu Chengtao C Wu Min M Wu Xiaoyu X Wan Lingfeng L Zhu Xuejun X

Cell proliferation 20190723 5

<h4>Objectives</h4>MicroRNAs are powerful regulators in hepatocellular carcinoma (HCC) tumorigenesis. MicoRNA-191 (miR-191) has been reported to play an important role in HCC, However, the regulatory mechanism is still unclear. In this study, we investigated the role of miR-191 in HCC and studied its underlying mechanisms of action.<h4>Materials and methods</h4>The expression of miR-191 in HCC tissues was determined by quantitative real-time PCR (qRT-PCR). The role of miR-191 in HCC cells was ex ...[more]

PMID: 31334580

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Project description:hsa-miR-191 is highly expressed in hepatocellular carcinoma (HCC), but the factors regulating this elevated expression are unknown. This study aimed to investigate the epigenetic mechanisms of increased hsa-miR-191 expression by analyzing the relationship between the DNA methylation status of hsa-miR-191 and miR-191 expression. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing PCR, Northern blot, and quantitative real-time PCR were performed to examine hsa-miR-191 methylation and expression levels. Western blot, transwell, and scratch assays were performed to examine the function and molecular mechanisms of hsa-miR-191. Approximately 58.9% of hsa-miR-191 expression was higher in HCC tissues than in adjacent noncancerous tissues; this high expression was associated with poor prognosis. The hypomethylation observed in some HCC cell lines and HCC tissues was correlated with the hsa-miR-191 expression level. This correlation was validated by treatment with the 5-aza-DAC demethylation agent. The level of hypomethylation was 63.0% in 73 clinical HCC tissue samples and was associated with increased (2.1-fold) hsa-miR-191 expression. The elevated expression of hsa-miR-191 in the SMMC-771 HCC cell line induced the cells to transition into mesenchymal-like cells; they exhibited characteristics such as loss of adhesion, down-regulation of epithelial cell markers, up-regulation of mesenchymal cell markers, and increased cell migration and invasion. Inhibiting hsa-miR-191 expression in the SMMC-7721 cell line reversed this process (as assessed by cell morphology and cell markers). Furthermore, hsa-miR-191 probably exerted its function by directly targeting TIMP metallopeptidase inhibitor 3 and inhibiting TIMP3 protein expression. Our results suggest that hsa-miR-191 locus hypomethylation causes an increase in hsa-miR-191 expression in HCC clinical tissues and that this expression induces HCC cells to transition into mesenchymal-like cells.

Dataset Information

MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis.

Publications

MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis.

Similar Datasets

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