Molecular Mechanism Of ZNF384 In Promoting The Proliferation Of Hepatocellular Carcinoma

Background:Hepatocellular carcinoma(HCC)is a multi-gene drived malignant tumor with highly heterogeneous.The ZNF384 gene encodes a transcription factor that binds to and regulates the extracellular matrix genes MMP1,MMP3,MMP7 and COL1A1 promoters.Numerous studies have shown that ZNF384 is involved in the development of acute B lymphocytic leukemia through gene rearrangement.ZNF384 is an overexpressed gene with high frequency alterations in HCC,while the study about ZNF384 function in HCC is vacant.Method:In this study,the expression level of ZNF384 in HCC was analyzed through immunohistochemical staining(IHC).We also constructed ZNF384 knockdown and knockout HCC cell lines using short hairpin RNA(shRNA)and CRISPR/Cas9 systems.And MTS,clone formation,5-ethynyl-20-deoxyuridine(EdU)assay,flow cytometry and xenograft mouse model were used to evaluate the effects of ZNF384 on cell proliferation.Western blot analysis and dual-luciferase reporter assay was performed to explore the potential molecular mechanism.Result:We found that the overexpression of ZNF384 in HCC and elevated ZNF384 expression in HCC tissues was significantly correlated with tumor recurrence(P=0.0181).Kaplan-Meier survival analysis revealed that the high expression levels of ZNF384 was correlated with poor overall survival(P=0.0003).Down-regulated the expression of ZNF384 suppressed the HCC cells proliferation by suppressing the expression of Cyclin D1.Conclusion:These findings suggest that ZNF384 is highly expressed in HCC and is closely related to the prognosis of patients.Moreover,ZNF384 affects the cell proliferation ability of HCC cells by regulating the expression of Cyclin D1.