Effect Of DNAJC1 On Malignant Biological Behaviors Of Liver Cancer And Its Mechanism

Background:Liver cancer is one of the most common malignant tumors in the world,and the number of new liver cancer cases in China accounts for 50%of the total number of new cases in the world each year.Studies have shown that DNAJ protein family play an important role in the occurrence and development of a variety of tumors.However,the expression and mechanism of DNAJC1 in liver cancer remain unclear.Methods:The expression level,prognostic value,methylation level,correlation of immune cell infiltration and biological function of DNAJC1 in liver cancer were analyzed by bioinformatics.The expression levels of DNAJC1in normal liver cell line LO₂ and liver cancer cell lines（Hep G2,MHCC97H,Huh7）were verified by quantitative real-time PCR（q RT-PCR）and Western blot.The expression levels of DNAJC1 in liver cancer tissues and adjacent tissues were analyzed by immunohistochemistry.DNAJC1 knockdown cell model was established by small interfering ribonucleic acid（si RNA）transfection assay.The effect of DNAJC1 knockdown on malignant behavior of liver cancer cells was detected by CCK-8 assay,clony formation assay,wound healing assay,transwell assay,Hoechst 33342 assay and flow cytometry,respectively.Finally,the expression of related signaling pathway proteins were verified by Western blot.Results:DNAJC1 is highly expressed in liver cancer and significantly associated with prognosis of liver cancer patients.Furthermore,DNAJC1 is hypomethylated in the genome of liver cancer patients.In addition,knockdown of DNAJC1 expression level can inhibit the proliferation,migration and invasion of liver cancer cells and promote cell apoptosis.Finally,compared with negative control group,the expression levels of E-cadherin,PARP,p21,p53,p-p53（Ser20）and Bax were significantly increased,and the expression levels of N-cadherin,MMP9,Vimentin,Snai1 and Bcl-2 were significantly decreased after DNAJC1 knockdown.Conclusions:DNAJC1 may mediate the proliferation,migration,invasion and apoptosis of liver cancer cells through p53 and EMT signaling pathways.DNAJC1 may be a new molecular target for the diagnosis,prognosis and treatment of liver cancer.