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MiR-191: an emerging player in disease biology.

ABSTRACT: Specific microRNAs have emerged as key players in disease biology by playing crucial role in disease development and progression. This review draws attention to one such microRNA, miR-191 that has been recently reported to be abnormally expressed in several cancers (>20) and various other diseases like diabetes-type 2, Crohn' s, pulmonary hypertension, and Alzheimer' s. It regulates important cellular processes such as cell proliferation, differentiation, apoptosis, and migration by targeting important transcription factors, chromatin remodelers, and cell cycle associated genes. Several studies have demonstrated it to be an excellent biomarker for cancer diagnosis and prognosis leading to two patents already in its kitty. In this first review we summarize the current knowledge of the regulation, functions and targets of miR-191 and discuss its potential as a promising disease biomarker and therapeutic target.

SUBMITTER: Nagpal N

PROVIDER: S-EPMC4005961 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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miR-191: an emerging player in disease biology.

Nagpal Neha N Kulshreshtha Ritu R

Frontiers in genetics 20140423

Specific microRNAs have emerged as key players in disease biology by playing crucial role in disease development and progression. This review draws attention to one such microRNA, miR-191 that has been recently reported to be abnormally expressed in several cancers (>20) and various other diseases like diabetes-type 2, Crohn' s, pulmonary hypertension, and Alzheimer' s. It regulates important cellular processes such as cell proliferation, differentiation, apoptosis, and migration by targeting im ...[more]

PMID: 24795757

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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

MiR-191: an emerging player in disease biology.

Publications

miR-191: an emerging player in disease biology.

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