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

• Published in: Frontiers of medicine Vol. 9; no. 3; pp. 331 - 343
• Main Authors: Tsang, Felice Ho-Ching, Au, Sandy Leung-Kuen, Wei, Lai, Fan, Dorothy Ngo-Yin, Lee, Joyce Man-Fong, Wong, Carmen Chak-Lui, Ng, Irene Oi-Lin, Wong, Chun-Ming
• Format: Journal Article
• Language: English
• Published: Beijing Higher Education Press 01.09.2015; Springer Nature B.V
• Subjects: Carcinoma, Hepatocellular - genetics; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; cytoskeletal reorganization; Down-Regulation; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; hepatocellular carcinoma; Humans; Liver cancer; Liver Neoplasms - genetics; Medicine; Medicine & Public Health; metastasis; microRNA; MicroRNAs; MicroRNAs - metabolism; Motility; Research Article; Signal Transduction - genetics; microRNA; cytoskeletal reorganization; metastasis; hepatocellular carcinoma
• ISSN: 2095-0217; 2095-0225
• DOI: 10.1007/s11684-015-0409-8

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.