A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer
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Wen Chen1, Wenrong He3, Hongbing Cai4, Bicheng Hu1, Caishang Zheng2, Xianliang Ke2, Li Xie2, Zhenhua Zheng2, Xinxing Wu1 and Hanzhong Wang2
1State Key Laboratory of Virology, Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
3Department of Gynaecology and Obstetrics, The First People’s Hospital of Jingzhou, Yangtze University, Jingzhou 434000, China
4Department of Gynecologic Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Xinxing Wu, email: [email protected]
Zhenhua Zheng, email: [email protected]
Keywords: A-to-I RNA editing, BLCAP gene, cervical carcinogenesis, STAT3, YXXQ motif
Received: December 28, 2016 Accepted: March 21, 2017 Published: April 11, 2017
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.
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