Open AccessThe impact of the RBM4-initiated splicing cascade on modulating the carcinogenic signature of colorectal cancer cells
Author(s) -
Ji-Ping Lin,
Yuan Chii Lee,
Yu Chih Liang,
Yang C. Fann,
Kory R. Johnson,
Ying Lin
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep44204
Subject(s) - rna splicing , intron , exon , biology , cancer research , alternative splicing , carcinogenesis , rna seq , colorectal cancer , splicing factor , rna , transcriptome , gene expression , cancer , genetics , gene
A growing body of studies has demonstrated that dysregulated splicing profiles constitute pivotal mechanisms for carcinogenesis. In this study, we identified discriminative splicing profiles of colorectal cancer (CRC) cells compared to adjacent normal tissues using deep RNA-sequencing (RNA-seq). The RNA-seq results and cohort studies indicated a relatively high ratio of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1 − 4 ) and intron 2-retained SRSF6 (SRSF6 +intron 2 ) transcripts in CRC tissues and cell lines. Nova1 variants exhibited differential effects on eliminating SRSF6 expression in CRC cells by inducing SRSF6 +intron 2 transcripts which were considered to be the putative target of alternative splicing-coupled nonsense-mediated decay mechanism. Moreover, the splicing profile of vascular endothelial growth factor (VEGF)165/VEGF165b transcripts was relevant to SRSF6 expression, which manipulates the progression of CRC calls. These results highlight the novel and hierarchical role of an alternative splicing cascade that is involved in the development of CRC.