KLF4 Inhibits Proliferation And Invasion In HCC Cells And Associates With The Prognosis Of Patients In Hepatocellular Carcinoma

Objective Hepatocellular carcinoma(HCC)is one of the most common malignant cancers.KLF4 plays an important role in process of tumor growth,proliferation,differentiation,and apoptosis.However,the role of KLF4 in hepatocellular carcinoma and the relationship between KLF4 and prognosis of hepatocellular carcinoma have not been fully clarified.The research aimed to explore the prognostic significance of KLF4 expression in hepatocellular carcinoma's(HCC)patients,and the potential mechanism of KLF4 inhibiting proliferation and invasion in hepatocellular carcinoma cells.Methods The expression level of KLF4 on tissues microarray was detected by immunohistochemical staining,and comparative analysis of overall survival(OS)and recurrence-free survival(RFS)are made in patients with low KLF4 expression and high KLF4 expression.The prognostic nomograms were employed to evaluate the predictive accuracy for KLF4.Western blot and q PCR were used to detect the expression level of KLF4 in HCC cell lines.CCK-8 assay,colony formation assay,cell wound scratch experiment and transwell experiment were performed to detect the effects of KLF4 on the growth,proliferation,migration and invasion of HCC through upregulating or knockeddown KLF4.Western blot and q PCR were used to detect the associated protein of EMT in HCC cells.Results There exited some correlation between KLF4 expression and serum AFP levels,vascular invasiveness,and BCLC stage.Patients with high KLF4 expression had longer OS and RFS compared to patients with low KLF4 expression,which showed KLF4 can be a prognostic marker in HCC patients.Compared with the control group,PLC/PRF/5 and Huh7 cells with stable overexpression of KLF4 had lower cell growth and proliferation rate,lower clone formation number,slower migration speed and reduced cellular invasion number.SMMC-7721 cells with sh RNA of KLF4 had higher cell growth and proliferation rate,larger clone formation number,faster migration speed and larger cellular invasion number compared with the control group.The results show KLF4 can inhibit the proliferation and invasion ability of HCC cells.Western blot and q PCR assay showed KLF4 blocked HCC EMT by upregulating E-cadherin and downregulating Ncadherin and vimentin.Conclusions KLF4 expression level is correlated with the prognosis of patients with hepatocellular carcinoma after curative resection.KLF4 inhibits the proliferation and invasion ability of hepatocellular carcinoma cells.The suppressive effect of KLF4 on proliferation and invasion possibly depends on blocking the epithelial mesenchymal transformation in hepatocellular carcinoma cells.