Downregulation of SSR2 enhanced the sensitivity of hepatocellular carcinoma cells to cisplatin through Hippo pathway

Abstract

Abstract Background Chemotherapy resistance is an obstacle to promote the survival of patients with hepatocellular carcinoma (HCC). Therefore, it is essential to find out the promising therapeutic targets to enhance the sensitivity of chemotherapy in HCC.Methods qPCR and western blotting assay were used to examine the expression of signal sequence receptor subunit (SSR2). Colony formation, flow cytometry assay, anchorage independent growth assay and in vivo animal model were used to investigate the effect of SSR2 on resistance of HCC cells to DDP. Western blotting, Luciferase reporter gene technique were used to explore the molecular mechanism of SSR2 on resistance of HCC cells to DDP.Results We found signal sequence receptor subunit (SSR2) is significantly upregulated in HCC, which leads to poor survival. Further analysis showed Downregulation of SSR2 increased sensitivity of HCC cells to DDP. Mechanically, SSR2 inhibited the phosphorylation of YAP and promoted the transcription of Hippo signaling downstream genes. Finally, the inhibitor of Hippo pathway can suppress colony formation and tumorigenesis arousing by upregulation of SSR2.Conclusions Our study provided evidence SSR2 played an important role in HCC progression via Hippo pathway, thus targeting SSR2/Hippo pathway axis might be an effective strategy to overcome DDP resistance in HCC.