A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer

被引:46
作者
Chen, Wen [1 ]
He, Wenrong [3 ]
Cai, Hongbing [4 ]
Hu, Bicheng [1 ]
Zheng, Caishang [2 ]
Ke, Xianliang [2 ]
Xie, Li [2 ]
Zheng, Zhenhua [2 ]
Wu, Xinxing [1 ]
Wang, Hanzhong [2 ]
机构
[1] Wuhan Univ, State Key Lab Virol, Inst Med Virol, Sch Basic Med Sci, Wuhan 430071, Peoples R China
[2] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
[3] Yangtze Univ, Dept Gynaecol & Obstet, Peoples Hosp Jingzhou 1, Jingzhou 434000, Peoples R China
[4] Wuhan Univ, Zhongnan Hosp, Dept Gynecol Oncol, Wuhan 430071, Peoples R China
基金
中国国家自然科学基金;
关键词
A-to-I RNA editing; BLCAP gene; cervical carcinogenesis; STAT3; YXXQ motif; SIGNAL TRANSDUCER; INOSINE RNA; PROTEIN; APOPTOSIS; EXPRESSION; ADENOSINE;
D O I
10.18632/oncotarget.17034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bladder cancer-associated protein (BLCAP) gene is a highly conserved gene with tumor-suppressor function in different carcinomas. It is also a novel ADAR-mediated editing substrate undergoes multiple A-to-I RNA editing events. Although the anti-tumorigenic role of BLCAP has been examined in preliminarily studies, the relationship between BLCAP function and A-to-I RNA editing in cervical carcinogenesis still require further exploration. Herein, we analyzed the coding sequence of BLCAP transcripts in 35 paired cervical cancer samples using high-throughput sequencing. Of note, editing levels of three novel editing sites were statistically different between cancerous and adjacent cervical tissues, and editing of these three sites was closely correlated. Moreover, two editing sites of BLCAP coding region were mapped-in the key YXXQ motif which can bind to SH2 domain of STAT3. Further studies revealed that BLCAP interacted with signal transducer and activator of transcription 3 (STAT3) and inhibited its phosphorylation, while A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer cell lines. Our findings reveal that A-to-I RNA editing events alter the genetically coded amino acid in BLCAP YXXQ motif, which drive the progression of cervical carcinogenesis through regulating STAT3 signaling pathway.
引用
收藏
页码:39417 / 39429
页数:13
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