Published on June 13, 2017 in Oncotarget volume 8(24).

PubMed ID: 28455960

DOI: 17034

Abstract:

Bladder cancer-associated protein (BLCAP) gene is a highly conserved gene withtumor-suppressor function in different carcinomas. It is also a novel ADAR-mediatedediting substrate undergoes multiple A-to-I RNA editing events. Although theanti-tumorigenic role of BLCAP has been examined in preliminarily studies, therelationship between BLCAP function and A-to-I RNA editing in cervicalcarcinogenesis still require further exploration. Herein, we analyzed the codingsequence of BLCAP transcripts in 35 paired cervical cancer samples usinghigh-throughput sequencing. Of note, editing levels of three novel editing siteswere statistically different between cancerous and adjacent cervical tissues, andediting of these three sites was closely correlated. Moreover, two editing sites ofBLCAP coding region were mapped-in the key YXXQ motif which can bind to SH2 domainof STAT3. Further studies revealed that BLCAP interacted with signal transducer andactivator of transcription 3 (STAT3) and inhibited its phosphorylation, while A-to-IRNA editing of BLCAP lost the inhibition to STAT3 activation in cervical cancer celllines. Our findings reveal that A-to-I RNA editing events alter the geneticallycoded amino acid in BLCAP YXXQ motif, which drive the progression of cervicalcarcinogenesis through regulating STAT3 signaling pathway.