Heterochromatin Protein HP1γ Promotes Colorectal Cancer Progression and Is Regulated by miR-30a

被引：103

作者：

Liu, Ming ^{[1
]}

Huang, Feifei ^{[1
,2
]}

Zhang, Dan

Ju, Junyi ^{[1
]}

Wu, Xiao-Bin ^{[2
]}

Wang, Ying ^{[1
]}

Wang, Yadong ^{[1
]}

Wu, Yupeng ^{[1
]}

Nie, Min ^{[1
]}

Li, Zhuchen ^{[1
]}

Ma, Chi ^{[1
]}

Chen, Xi ^{[1
]}

Zhou, Jin-Yong ^{[2
]}

Tan, Renxiang ^{[1
]}

Yang, Bo-Lin ^{[2
]}

Zen, Ke ^{[1
]}

Zhang, Chen-Yu ^{[1
]}

Chen, Yu-Gen ^{[2
]}

Zhao, Quan ^{[1
]}

机构：

[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210046, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China

来源：

CANCER RESEARCH | 2015年 / 75卷 / 21期

基金：

中国国家自然科学基金;

关键词：

GLOBIN GENE-EXPRESSION; HISTONE H3; DROSOPHILA-MELANOGASTER; CHROMOSOMAL-PROTEIN; PROSTATE-CANCER; BREAST-CANCER; HP1; PROTEINS; LYSINE; 9; MICRORNA; METHYLATION;

D O I：

10.1158/0008-5472.CAN-14-3735

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Colorectal cancer pathogenesis remains incompletely understood. Here, we report that the heterochromatin protein HP1 gamma is upregulated commonly in human colorectal cancer, where it promotes cell proliferation in vitro and in vivo. Gene-expression and promoter-binding experiments demonstrated that HP1 gamma directly regulated CDKN1A (p21(Waf1/Cip1)) in a manner associated with methylation of histone H3K9 on its promoter. We identified miR-30a as a tumor-suppressive microRNA that targets HP1 gamma in vitro and in vivo to specifically suppress the growth of colorectal cancer in mouse xenograft models. MiR-30a was widely downregulated in primary human colorectal cancer tissues, where its expression correlated inversely with high levels of HP1 gamma protein. Our results identify a new miR-30a/HP1 gamma/p21 regulatory axis controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities. (C) 2015 AACR.

引用

页码：4593 / 4604

页数：12

共 42 条

[1] Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain [J].