Biological functional role of miR-146a-5p on cell growth and caspase-3/7 activity via targeting TRAF6 in hepatocellular carcinoma

Background: We have previously reported that miR-146a-5p (previous ID: miR-146a) level was significantly reduced in hepatocellular carcinoma (HCC) tissues and its biological function could be partially exerted via targeting epidermal growth factor receptor (EGFR). However, miR-146a-5p could play its biological role via other targets. The relationships between miR-146a-5p and tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) have been investigated in several diseases, but, their associations remain unclarified in HCC. Thus, the objective of the present study was to assess the biological function of miR-146a-5p via targeting TRAF6 in HCC. Methods: In silico, the prediction analysis of the complementary sequences between miR-146a-5p and the 3'-untranslated region of TRAF6 was performed. Further experiments in vitro on HepG2 and Hep3B cell lines were carried out to validate the biological function of miR-146a-5p, as well as TRAF6 with the assays of cell viability, proliferation, apoptosis and caspase-3/7 activity. Finally, the clinical role of miR-146a-5p and TRAF6 in HCC tissues was validated using the data downloaded from the cancer genome atlas (TCGA). Results: Complementary sequences between miR-146a-5p and the 3'-untranslated regions of TRAF6 were confirmed in silico. In both HepG2 and Hep3B cell lines, miR-146a-5p mimic and TRAF6 silencing repressed the cell growth as demonstrated by different approaches. Furthermore, miR-146a-5p mimic and TRAF6 knock-down induced cell apoptosis and caspase-3/7 activity. The biological effect was more potent when generated from TRAF6 siRNA as compared to that from miR-146a-5p mimic. Additionally, significantly down-regulated miR-146a was observed in 354 cases of HCC cases in TCGA database (P<0.001). The area under the curve (AUC) in receiver operating characteristic (ROC) curve reached 0.686 (95% CI: 0.628-0.744, P<0.001) for miR-146a to diagnose HCC. Conclusions: MiR-146a-5p might play its vital role in the carcinogenesis and progression of HCC partly via targeting TRAF6.