A Genetic Variant rs10251977 in Long Non-coding RNA EGFR-AS1 Creates a New Binding Site for miR-891b and Modulates the Expression of EGFR A/D Isoforms

Abstract Tyrosine kinase inhibitor (TKI) is one of the effective chemo-preventive approaches against tumors that deregulate EGFR pathway. About 80% of HNSCC patients overexpress EGFR, making TKI an effective treatment against this cancer. Recently a synonymous variant rs10251977 in exon 20 of EGFR reported to act as a prognostic marker in HNSCC. Analysis of this germline variant in blood samples of oral cancer patients showed a similar frequency in cases and controls. Further, in-silico analysis showed that this polymorphism creates binding site for miR-891b in EGFR-AS1. The EGFR-AS1 expression modulates the EGFR A/D isoforms through alternative splicing. Our bioinformatic analysis showed enrichment of alternative splicing marks H3K36me3 and presence of a few intronic polyA sites spanning around exon 15a and 15b of EGFR facilitating the skipping of exon 15b and thereby promoting the splicing of EGFR-A isoform. In addition, the presence of PTBP1 binding site in EGFR and EGFR-AS1 enhances the expression of EGFR- A isoform by preventing the premature termination. Expression profiling of EGFR-AS1 along with miR-891b level and rs10251977 polymorphism status in oral cancer patients may be useful for targeted therapy