miR-141 inhibits proliferation, migration and invasion in human hepatocellular carcinoma cells by directly downregulating TGF beta R1

摘要

MicroRNAs (miRNAs) have been demonstrated to have crucial roles in modulating various human cancers. The present study examined the involvement of miR-141 in modulating the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. Notably, the results demonstrated that miR-141 was significantly downregulated in primary liver tumor tissues from patients compared with adjacent non-tumor tissues. Overexpression of miR-141 in HCC cells robustly impaired migration and invasion and suppressed proliferation in vitro, by arresting cells at the G2/M phase. Further analyses revealed that miR-141 overexpression downregulated transforming growth factor beta receptor 1 (TGF beta R1) by directly binding to its 3 ' untranslated region. In addition, the mRNA and protein levels of TGF beta R1 were both significantly increased in HCC patient tissues compared with matched adjacent non-tumor tissues. Silencing of TGF beta R1 produced similar effects in vitro to miR-141 overexpression. Furthermore, the downstream protein SMAD family member 2 was downregulated following overexpression of miR-141 or silencing of TGF beta R1. These findings indicated that miR-141 inhibited HCC cell proliferation and invasion by directly downregulating TGF beta R1 and its downstream signaling cascade, providing insights into a potential novel strategy for HCC therapy.