Abstract 1845: Cooperative function between miR-142-3p and miR-142-5p in hepatocellular carcinoma.

Abstract MicroRNAs (miRNAs) are small non-coding RNAs regulate gene expression at post-transcriptional level and involved in a wide range of biological processes. Aberrant expressions of miRNA have subsequently been identified in different types of cancers, including hepatocellular carcinoma (HCC). Due to their abilities in targeting multiple tumor suppressor genes and oncogenes, miRNAs are speculated to involve in carcinogenesis. From a miRNA profiling study and subsequent qRT-PCR validation, miR-142-3p and miR-142-5p were found to be significantly down-regulated in HCC tumors versus adjacent non-tumor and their expressions were further decreased in corresponding venous metastases. Functionally, HCC cells stably overexpressing miR-142 showed significant reduction in cell migration and invasion, but not in cell proliferation and colony formation of HCC cells. Overexpression of miR-142 also significantly reduced stress fibre formation and led to cell shrinkage in HCC cells as revealed by immunofluorescent staining (IF) and scanning electron microscope (SEM). Interestingly, transient overexpression of either miR-142-3p or miR-142-5p alone using miRNA-precursors reduced the migration of HCC cells. Whereas, overexpression of both the miR-142-3p and miR-142-5p precursors further inhibited cell migration synergistically, suggesting that miR-142-3p and miR-142-5p may function cooperatively to regulate cell movement. MiR-142-3p and mir-142-5p are mature miRNAs derived from the 3’ and 5’ strand of precursor-miR-142 respectively, in which they possess totally different seed sequences and hence distinct pools of target genes. Based on the bioinformatic prediction from Targetscan 5.0 algorithm, a total of 696 genes were predicted as putative targets of miR-142-3p and miR-142-5p. The biological relevancies of their targets were further revealed by using the DIANA mirPath enrichment analysis. Intriguingly, downstream gene targets of miR-142-3p and miR-142-5p have been highly enriched in pathways regulating cell movement, such as the regulation of actin cytoskeleton (p=6.30e-08), adherens junction (p=2.71e-06) and focal adhesion (p=1.80e-03). Until recently, little was known about the functional relationships between the -3p and -5p mature miRNA species derived from the same precursor-miRNA and their biological relevance in cancer biology. In this study, we have illustrated the coordination between the mature miR-142-3p and miR-142-5p. It is postulated that the down-regulation of miR-142 in HCC may lead to the de-repression of components regulating cell movements and eventually promote cell migration, invasion or even metastasis of HCC. Citation Format: Felice Hoching Tsang, Oi Lin Ng, Chun Ming Wong. Cooperative function between miR-142-3p and miR-142-5p in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1845. doi:10.1158/1538-7445.AM2013-1845