Tumor metastasis portrayed the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumors, including hepatocellular carcinoma (HCC). In this regard, anti-metastatic genes have a great potential for metastasis inhibition. Recent evidence pointed to a role of Breast cancer metastasis suppressor 1 (BRMS1) in suppression of metastasis of several types of cancers, whereas the regulation of BRMS1 in HCC remains unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and evaluated the functional binding of miRNAs to BRMS1 mRNA using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, we only detected significant expression of miR-626, miR-1289 and miR-423 in HCC specimens. Specifically, we found that only miR-423 significantly inhibited protein translation of BRMS1 via specific binding to 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower levels of BRMS1 and significantly higher levels of miR-423 in the HCC specimens, relative to paired adjacent non-tumor liver tissue. Furthermore, BRMS1 and miR-423 levels were correlated inversely. Overexpression of miR-423 significantly decreased BRMS1 levels and promoted HCC cell invasion, while depletion of miR-423 significantly increased BRMS1 levels and inhibited HCC cell invasion. This study sheds light on miR-423 as a crucial factor that enhances HCC cell invasiveness, and suggests miR-423 as a promising therapeutic target for HCC treatment.
Keywords: Hepatocellular carcinoma (HCC); breast cancer metastasis suppressor 1 (BRMS1); miR-423.