Splice isoforms as therapeutic targets for colorectal cancer

Koh Miura, Wataru Fujibuchi, Michiaki Unno

Research output: Contribution to journalReview articlepeer-review

35 Citations (Scopus)

Abstract

Alternative pre-mRNA splicing allows exons of pre-mRNA to be spliced in different arrangements to produce functionally distinct mRNAs. More than 95% of human genes encode splice isoforms, some of which exert antagonistic functions. Recent studies revealed that alterations of the splicing machinery can cause the development of neoplasms, and understanding the splicing machinery is crucial for developing novel therapeutic strategies for malignancies. Colorectal cancer patients need novel strategies not only to enhance the efficacy of the currently available agents but also to utilize newly identified therapeutic targets. This review summarizes the current knowledge about the splice isoforms of VEGFA, UGT1A, PXR, cyclin D1, BIRC5 (survivin), DPD, K-RAS, SOX9, SLC39A14 and other genes, which may be possible therapeutic targets for colorectal cancer. Among them, the VEGFA splice isoforms are classified into VEGFAxxx and VEGFAxxxb, which have proangiogenic and antiangiogenic properties, respectively; UGT1A is alternatively spliced into UGT1A1 and other isoforms, which are regulated by pregnane X receptor isoforms and undergo further splicing modifications. Recently, the splicing machinery has been extensively investigated and novel discoveries in this research field are being reported at a rapid pace. The information contained in this review also provides suggestions for how therapeutic strategies targeting alternative splicing can be further developed.

Original languageEnglish
Article numberbgs347
Pages (from-to)2311-2319
Number of pages9
JournalCarcinogenesis
Volume33
Issue number12
DOIs
Publication statusPublished - 2012 Dec

ASJC Scopus subject areas

  • Cancer Research

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