SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter

被引：39

作者：

Shuai, Wendi ^{[1
]}

Wu, Jiangxue ^{[1
]}

Chen, Shuai ^{[1
]}

Liu, Ranyi ^{[1
]}

Ye, Zhihua ^{[1
]}

Kuang, Chunmei ^{[1
]}

Fu, Xiang ^{[1
]}

Wang, Gaoyuan ^{[1
]}

Li, Yingchang ^{[1
]}

Peng, Qihua ^{[1
]}

Shi, Wei ^{[1
]}

Li, Yizhuo ^{[1
]}

Zhou, Qianghua ^{[1
]}

Huang, Wenlin ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2018年 / 422卷

基金：

中国国家自然科学基金;

关键词：

SUV39H2; SLIT1; Colorectal cancer; Proliferation; Metastasis; HISTONE MODIFYING ENZYMES; DNA METHYLATION; UP-REGULATION; GENE; H3; METHYLTRANSFERASES; HETEROCHROMATIN; ROUNDABOUT; EXPRESSION; COLON;

D O I：

10.1016/j.canlet.2018.02.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Suppressor of variegation 3-9 homolog 2 (SUV39H2) is a member of the SUV39H subfamily of lysine methyltransferases. Its role in colorectal cancer (CRC) proliferation and metastasis has remained unexplored. Here, we determined that SUV39H2 was upregulated in CRC tissues compared with that in adjacent non-neoplastic tissues. Further statistical analysis revealed that high SUV39H2 expression was strongly associated with distant metastasis (P = 0.016) and TNM stage (P = 0.038) and predicted a shorter overall survival (OS; P = 0.018) and progression-free survival (PFS; P = 0.018) time for CRC patients. Both in vitro and in vivo assays demonstrated that ectopically expressed SUV39H2 enhanced CRC proliferation and metastasis, while SUV39H2 knockdown inhibited CRC proliferation and metastasis. A molecular screen of SUV39H2 targets found that SUV39H2 negatively regulated the expression of SLIT guidance ligand 1 (SLIT1). Moreover, rescue assays suggested that SLIT1 could antagonize the function of SUV39H2 in CRC. Mechanistic studies indicated that SUV39H2 can directly bind to the SLIT1 promoter, suppressing SLIT1 transcription by catalyzing histone H3 lysine 9 (H3K9) tri-methylation. In summary, we propose that SUV39H2 can predict CRC patient prognosis and stimulate CRC malignant phenotypes via SLIT1 promoter tri-methylation. (C) 2018 Elsevier B.V. All rights reserved.

引用

页码：56 / 69

页数：14

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