Study Of Mechanism And Function Of MDIG In Hepatocellular Carcinoma

MDIG is associated with the development and prognosis of many types of human cancers,such as esophageal cancer,gastic cancer,colon cancer,and lung cancer,etc.although the mechanisms and functions of MDIG in hepatocellular carcinoma is unclear.In this study,we find that ectopic overexpression and inhibition of IKZF1 in hepatocellular carcinoma affect the expression of MDIG,MDIG is negatively regulated by IKZF1 with m RNA expression levels.The results of Ch IP showed that IKZF1 regulates expression of MDIG by directly binding to the promoter region of MDIG at transcriptional level.In vitro,MDIG overexpression substantially promoted HCC cell proliferation,cell migration and spreading,whereas knockdown of MDIG would reverse above-mentioned effect.MDIG effects on tumor cell growth were further demonstrated in a tumor xenograft model.Furthermore,MDIG was also found to be closely related to the sorafenib resistance of HCC cells in vitro.MDIG serves as the histone demethyltransferase,which had effects on the level of p21(CIP1/WAF1)via H3K9me3 expression in HCC.The results of chromatin immunoprecipitation showed H3K9me3 directly regulated the transcription level of p21(CIP1/WAF1).In this study,we analyze MDIG expression in 155 pairs of human primary HCC and adjacent tissues by immunohistochemical staining(IHC),and find that MDIG is expressed at high levels in hepatocellular carcinoma samples,As to clinicopathological correlation,MDIG overexpression was significantly associated with the histological grade,hepatitis B surface antigen(HBs Ag)levels.These findings suggest that MDIG promotes hepatocellular carcinoma cell proliferation in hepatocellular carcinoma,MDIG could serve as a potential therapeutic target.