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MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma and exhibit synergistic effects on cell motility

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Frontiers of Medicine 2015年第3期9卷 331-343页

作者： felice ho-ching tsang sandy leung-kuen au lai wei dorothy ngo-yin fan joyce man-fong lee carmen chak-lui wong irene oi-lin ng chun-ming wong State Key Laboratory for Liver Research and Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong HongKong SAR China

MicroRNAs （miRNAs）, an important class of small non-coding RNAs, regulate gene expression at the post-transcriptional level, miRNAs are involved in a wide range of biological processes and implicated in different diseases, including cancers. In this study, miRNA profiling and qRT-PCR validation revealed that miR-142-3p and miR-142-5p were significantly downregulated in hepatocellular carcinoma （HCC） and their expression levels decreased as the disease progressed. The ectopic expression of miR-142 significantly reduced HCC cell migration and invasion. Overexpression of either miR-142-3p or miR-142-5p suppressed HCC cell migration, and overexpression of both synergistically inhibited cell migration, which indicated that miR-142-3p and miR-142-5p may cooperatively regulate cell movement, miR-142-3p and miR-142-5p, which are mature miRNAs derived from the 3＇- and 5＇-strands of the precursor miR-142, target distinct pools of genes because of their different seed sequences. Pathway enrichment analysis showed a strong association of the putative gene targets of miR-142-3p and miR-142-5p with several cell motility-associated pathways, including those regulating actin cytoskeleton, adherens junctions, and focal adhesion. Importantly, a number of the putative gene targets were also significantly upregulated in human HCC cells. Moreover, overexpression of miR-142 significantly abrogated stress fiber formation in HCC cells and led to cell shrinkage. This study shows that mature miR-142 pairs collaboratively regulate different components of distinct signaling cascades and therefore affects the motility of HCC cells.

关键词： hepatocellular carcinoma microRNA metastasis cytoskeletal reorganization

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