The Role And Mechanism Of Histone Methyltransferase KMT2C In Prostate Cancer Progression

Prostate cancer is one of the most common malignant tumors in elderly men,which seriously threatens the life and health of elderly men.At the same time,due to the large heterogeneity of prostate cancer,patients’ response to treatment is uneven,and the prognosis is significantly different.Therefore,it is necessary to further study the pathogenesis of prostate cancer.KMT2C is an important histone methyltransferase,which is involved in the epigenetic regulation of cells and plays an important role in the occurrence and development of various tumors.In this study,the expression changes,biological functions and mechanisms of KMT2C in prostate cancer were investigated by using immunohistochemistry,qPCR,western blot,RNA seq,ChIP-qPCR and other experimental techniques.We first analyzed the data in multiple existing public databases,and further verified with the clinical specimen data of prostate cancer in our hospital,found that compared with benign prostate tissue,KMT2C transcription level and protein expression in prostate tissue volume are increased significantly,and its expression level is closely related to the patients with tumor stage and progress.Therefore,the biological function changes of prostate cancer cells after KMT2C knockdown were detected in vitro and in vivo.In vitro studies using a variety of prostate cancer cell lines,it was found that the proliferation,clonal formation and migration of tumor cells were significantly decreased after the KMT2C knockdown.Consistent with in vitro studies,in vivo xenograft tumor experiments in mice also showed that KMT2C knockdown can significantly reduce the growth rate of xenograft tumor.In terms of mechanism studies,we confirmed through RNA seq,western blot assay and Chip-qPCR that KMT2C in prostate cancer can affect the expression of CLDN8 and ITGAV genes by regulating the activity of gene enhancers,thus changing the activity of intracellular MAPK/ERK signaling pathway and the occurrence of epithelial-mesenchymal transformation.In conclusion,this study demonstrates that KMT2C in prostate cancer may affect the biological function of tumor cells by regulating the expression of CLDN8 and ITGAV genes.The molecular mechanism may be that the changes in CLDN8 and ITGAV gene expression may affect the activity of the intracellular MAPK/ERK signaling pathway and epithelial-mesenchymal transformation.