The RNA-binding protein PCBP2 facilitates gastric carcinoma growth by targeting miR-34a

被引:40
作者
Hu, Cheng-En [1 ]
Liu, Yong-Chao [1 ]
Zhang, Hui-Dong [2 ]
Huang, Guang-Jian [1 ]
机构
[1] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China
[2] Shanghai Childrens Med Ctr, Dept Gen Surg, Shanghai, Peoples R China
关键词
PCBP2; Gastric cancer; miR-34a; Apoptosis; HISTONE DEACETYLASE SIRT6; CANCER CELLS; POLY(RC)-BINDING PROTEIN-2; EXPRESSION; TRANSLATION; TRANSCRIPTION; SUPPRESSES; RECEPTORS; GLIOMA; LOOP;
D O I
10.1016/j.bbrc.2014.04.124
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
Gastric carcinoma is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. However, the mechanism underling gastric cancer is still not fully understood. Here in the present study, we identify the RNA-binding protein PCBP2 as an oncogenic protein in human gastric carcinoma. Our results show that PCBP2 is up-regulated in human gastric cancer tissues compared to adjacent normal tissues, and that high level of PCBP2 predicts poor overall and disease-free survival. Knockdown of PCBP2 in gastric cancer cells inhibits cell proliferation and colony formation in vitro, whereas opposing results are obtained when PCBP2 is overexpressed. Our in vivo subcutaneous xenograft results also show that PCBP2 can critically regulate gastric cancer cell growth. In addition, we find that PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, we identify that miR-34a as a target of PCBP2, and that miR-34a is critically essential for the function of PCBP2. In summary, PCBP2 promotes gastric carcinoma development by regulating the level of miR-34a. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:437 / 442
页数:6
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