The Roles Of Histone Demethylase JMJD2D In Cholangiocarcinoma Cells Proliferation、Migration And Invasion

Histone demethylase JMJD2D(also known as KDM4D)is a member of the subfamily of histone demethylase JMJD2.Compared with other members of JMJD2 subfamily JMJD2A,JMJD2B,JMJD2C and JMJD2E,JMJD2D has its unique structure and plays an important role in the occurrence and development of prostate cancer,colorectal cancer and many other diseases.As a malignant disease,the incidence of cholangiocarcinoma is increasing year by year and the prognosis is extremely poor.To clarify the molecuLar mechanism of the occurrence and development of cholangiocarcinoma will provide an important theoretical basis for improving the clinical diagnosis and treatment of cholangiocarcinoma.Until now,the role of JMJD2D in cholangiocarcinoma remains unclear.In this study,we first established stable knock down JMJD2D cell lines in QBC939 and MZ-Chal cholangiocarcinoma cell lines by using small hairpin RNA technology,and then examined the effect of knock down JMJD2D on proliferation,migration and invasion of cholangiocarcinoma cells by using MTT,clone formation,scratch and Transwell assay.The resuLts showed that knocking down JMJD2D significantly inhibited the proliferation,clone formation,migration and invasion of cholangiocarcinoma cells.These resuLts suggest that JMJD2D may play an important role in promoting the development of cholangiocarcinoma.Further studies showed that down-reguLation of JMJD2D significantly inhibited the expression of c-Myc mRNA and protein and the activity of c-Myc gene promoter in cholangiocarcinoma cells.These resuLts suggest that JMJD2D promotes the expression of c-Myc protein at the transcriptional level,and JMJD2D may promote the proliferation,migration and invasion of cholangiocarcinoma by reguLating the expression of c-Myc.In summary,our study is the first to identify the role of histone demethylase JMJD2D in promoting proliferation,migration and invasion of bile duct cancer cells,which may be accomplished by reguLating the expression of c-Myc protein.These resuLts suggest that JMJD2D may be a new target for the treatment of cholangiocarcinoma.