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

Abstract

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.

Identification of BLCAP as a novel STAT3 interaction partner in bladder cancer

“…While we were revising this article, a study was published that not only supports our observations, but also clarifies some of the unusual aspects of the Blcap biology we have reported [ 37 ]. In this study, Chen and colleagues showed that Blcap interacted with Stat3 in cervical cancer cell lines, supporting our own observation that Blcap interacts with Stat3 in bladder cancer.…”

Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications

“…40 In that regard, increased hyperediting of BLCAP has already been reported in HCC 44 and to a minor degree in brain, cervical, oral cavity and lung tumors. 45,46 Previous investigations revealed that BLCAP editing could affect the functions of several binding proteins such as RB 47 or STAT3 46 ; thereby, influencing proliferation and apoptotic signaling pathways. In HCC, experiments performed in SMMC_7721 and Focus liver cancer cell lines revealed that nt 5 editing confers a growth advantage, modulating the activation of AKT/mTOR signaling.…”

“…Technology, Icahn School of Medicine at Mount Sinai, New York, NY; 45 INSERM, UMR 1193, Paul-Brousse Hospital, Hepatobiliary Centre, Villejuif, France; 46 Innate Immunity Group, IGTP, Badalona, Spain; 47 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors.…”

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“…AZIN1 [94] and others [95]) they must be considered in toto in the context of oncogenesis. This is of immediate clinical relevance and several attempts are currently made to generate inhibitors of A-to-I deaminases as small molecules with anti-cancer activity [96,97].…”