KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation

被引：26

作者：

Fang, Yang ^{[1
,2
]}

Zhang, Dan ^{[3
]}

Hu, Tingting ^{[4
]}

Zhao, Hongyan ^{[1
,2
]}

Zhao, Xuan ^{[1
,2
]}

Lou, Zhefeng ^{[1
,2
]}

He, Yongshan ^{[5
]}

Qin, Wenzheng ^{[6
]}

Xia, Jianfu ^{[7
]}

Zhang, Xiaohua ^{[8
]}

Ye, Le-chi ^{[8
]}

机构：

[1] Minist Educ, Zhejiang Prov Key Lab Technol & Applicat Model Or, Key Lab Lab Med, Wenzhou, Peoples R China

[2] Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou, Peoples R China

[3] Wenzhou Med Univ, Dept Resp Med, Affiliated Hosp 1, Wenzhou, Peoples R China

[4] Wenzhou Med Univ, Dept Gastroenterol & Hepatol, Affiliated Hosp 1, Wenzhou, Peoples R China

[5] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Colorectal & Anal Surg, Sch Med, Shanghai, Peoples R China

[6] Fudan Univ, Zhongshan Hosp, Endoscopy Ctr, Shanghai, Peoples R China

[7] Wenzhou Cent Hosp, Dept Gen Surg, Wenzhou, Peoples R China

[8] Wenzhou Med Univ, Dept Colorectal & Anal Surg, Affiliated Hosp 1, Wenzhou 325015, Zhejiang, Peoples R China

来源：

CANCER MEDICINE | 2019年 / 8卷 / 07期

基金：

中国国家自然科学基金;

关键词：

cancer development; CTSZ; epigenetic modifier; KMT2A;

D O I：

10.1002/cam4.2226

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：3544 / 3552

页数：9

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