The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer

被引:45
|
作者
Shen, Yuzhou [1 ]
Pan, Xufeng [1 ]
Zhao, Heng [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Chest Hosp, Dept Thorac Surg, Shanghai 200030, Peoples R China
关键词
PHF8; Non-small cell lung cancer; Apoptosis; miR-21; LINKED MENTAL-RETARDATION; CLEFT LIP/CLEFT PALATE; RNA; GROWTH; GENE; TRANSCRIPTION; MICRORNA-21; MUTATIONS; BINDING;
D O I
10.1016/j.bbrc.2014.07.076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved in the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. Herein we report that PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up-regulated in human NSCLC tissues, and high PHF8 expression predicts poor survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung cancer cell proliferation and cellular transformation. We found that PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8 promotes lung cancer cell growth and survival by regulating miR-21. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:119 / 125
页数:7
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