The Role Of HNRNPC In The Proliferation,Invasion And Migration Of Hepatocellular Carcinoma And The Corresponding Mechanism

Objective: Hepatocellular carcinoma(HCC)is the fifth most common cancer among all cancers,and its fatality rate is the fourth most tumor-related death rate.Despite the increasing number of treatments being used for Hepatocellular carcinoma,the prognosis for patients with HCC remains poor.So we need to explore some new targets for the treatment of HCC.HNRNPC,a gene involved in alternative splicing,has been reported to be involved in the progression of a variety of tumors,but its role in HCC has not been reported.In this study,we will examine the differences in the expression of HNRNPC in HCC and para-tumor tissues.To analyze the relationship between the expression of HNRNPC and clinicopathological parameters and prognosis of patients with HCC.To explore the effect of HNRNPC on the proliferation,migration and invasion of hepatocellular carcinoma cells and its related mechanisms.Methods: The expression differences of HNRNPC in HCC and adjacent tissues were detected by western blotting and immunohistochemical staining.Chi-square test was used to analyze the relationship between HNRNPC expression and clinicopathological characters in patients with HCC.Cox regression model was used to analyze the risk factors affecting the prognosis of patients with HCC.By using lentivirus infection,the expression of HNRNPC in Huh-7 and HEP 3B cells was stably knocked down,and the effects of HNRNPC knockdown on the proliferation,invasion and migration of HCC cells were investigated by functional experiments in vitro.The effect of HNRNPC knockdown on the proliferation of hepatocellular carcinoma cells in vivo was studied by subcutaneous tumor-forming experiment in nude mice.Finally,the mechanism of HNRNPC regulating the proliferation,migration and invasion of HCC cells was further studied by Western blotting and flow cytometry.Results: Western blotting and immunohistochemical staining showed that the expression of HNRNPC in HCC tissues was higher than that in adjacent tissues.The expression of HNRNPC was positively correlated with tumor size and TNM stage.While the expression of HNRNPC was negatively correlated with the survival and prognosis of HCC patients.In vitro functional experiments showed that HNRNPC knockdown significantly inhibited the proliferation,invasion and migration of HCC cells.In addition,subcutaneous tumor-formation experiments in nude mice demonstrated that the silencing of HNRNPC significantly inhibited the proliferation of HCC cells in vivo.Mechanism studies have demonstrated that HNRNPC knockdown leads to limited proliferation,invasion and migration of HCC cells,which is partially achieved by inhibiting RAS /MAPK signaling pathway.Conclusion: HNRNPC is an oncogene,its abnormal expression is a factor promoting the progression of HCC,and it has the potential to be a new therapeutic target for HCC.