In conclusion, our results show that RhoC/ROCK2 may have a major effect on VM in HCC via ERK/MMPs signaling and might be a potential therapeutic target for the treatment of HCC.
Using a strategy to interpret kinase- substrate relations in HCC and to uncover predominant kinases in tumors, our results, revealed elevated kinase activities of Src family kinases (SFKs), PKCs, MAPKs, and ROCK2 in HCC, representatives of which were further validated in cell models and clinical HBV-positive HCC samples.
Inhibition of miR-448 significantly promoted cell invasion, while the effect of miR-448 up-regulation was reverse. miR-448 could regulate ROCK2 in hepatocellular carcinoma.
Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo.
Additionally, the upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced HCC migration and invasion.