KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation. (15th May 2019)

• Record Type: Journal Article
• Authors: Fang, Yang; Zhang, Dan; Hu, Tingting; Zhao, Hongyan; Zhao, Xuan; Lou, Zhefeng; He, Yongshan; Qin, Wenzheng; Xia, Jianfu; Zhang, Xiaohua; Ye, Le‐chi
• Is Part Of: Cancer medicine. Volume 8:Number 7(2019:Jul.)
• Page Start: 3544
• Page End: 3552
• Publication Date: 2019-05-15
• Subjects: cancer development -- CTSZ -- epigenetic modifier -- KMT2A; 616.994005
• DOI: 10.1002/cam4.2226
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Accumulating evidence supports the notion that epigenetic modifiers are abnormal in carcinogenesis and have a fundamental role in cancer progression. Among these aberrant epigenetic modifiers, the function of histone methyltransferase KMT2A in somatic tumors is not well known. By analyzing KMT2A expression in patient tissues, we demonstrated that KMT2A was overexpressed in colorectal cancer tissues in comparison with adjacent normal tissues and its expression was positively correlated with cancer stages. In KMT2A‐knockdown HCT116 and DLD1 cells, cell invasion and migration were consequently suppressed. In addition, KMT2A depletion effectively suppressed cancer metastasis in vivo. Mechanistically, cathepsin Z (CTSZ) was demonstrated to be an important downstream gene of KMT2A. Further studies showed that p65 could recruit KMT2A on the promoter region of the downstream gene CTSZ and knockdown of p65 could reduce the KMT2A on the promoter of CTSZ. Finally, our present study revealed that KMT2A epigenetically promotes cancer progression by targeting CTSZ, which has specific functions in cancer invasion and metastasis. Abstract : Accumulating evidence supports the notion that abnormalities in epigenetic modifiers are emerging as a fundamental role in cancer development. The histone methyltransferase KMT2A, a frequently aberrant epigenetic modifier in various tumors, has an undefined role in colorectal cancer (CRC). Our present study revealed that KMT2A epigenetically promotes cancer progression by targeting cathepsin Z (CTSZ), which has specific functions in cancer invasion and metastasis.