RhoE/ROCK signaling modulates chemoresistance in HCC through IL6/JAK2/STAT3 pathways

Abstract

Liver cancer (hepatocellular carcinoma, HCC) is a major malignancy worldwide and the second commonest fatal cancer in Southeast Asia and China including Hong Kong, due to the high prevalence of hepatitis B viral infection. HCC is highly chemoresistant, limiting treatment options to patients. There is an urgent need to delineate the underlying molecular mechanism of HCC chemoresistance so as to identify novel therapeutic targets for this aggressive cancer. Deregulation of Rho GTPase pathway is demonstrated to play important roles in HCC tumorigenesis. RhoE/Rnd3 belongs to the Rnd subfamily of the Rho GTPase which lacks the intrinsic GTPase activity. In our previous study, we have shown that RhoE is frequently downregulated in human HCCs and acts as a metastasis suppressor, whereas ROCK2 is upregulated in human HCCs. In this study, we aimed to investigate whether RhoE is also involved in the regulation of chemoresistance in HCC. Using short-hairpin RNA and ...