CRMP5-associated GTPase (CRAG) Is a candidate driver gene for colorectal cancer carcinogenesis

Abstract

Background/Aim: Certain chromosomal arms are clonally amplified in colorectal cancer (CRC) and may contain novel driver genes. The aim of this study was to identify a novel driver gene for colorectal cancer carcinogenesis on long arm of chromosome 7 and the clarify its biological function. Materials and Methods: We identified ArfGAP with GTPase domain, ankyrin repeat and PH domain 3 (AGAP3) as a putative driver gene using the CRC dataset in The Cancer Genome Atlas (TCGA). Biological functions of AGAP3 and CRMP5-associated GTPase (CRAG), a splicing variant of AGAP3, were explored by overexpression. AGAP3/CRAG expression in our cohort was examined by quantitative reverse transcription polymerase chain reaction. Clinical significance of AGAP3/CRAG expression in TCGA dataset, Gene Expression Omnibus datasets and our clinical cohort was evaluated. Results: AGAP3 expression was significantly increased in CRC and colorectal adenoma compared to normal tissue. CRAG overexpression up-regulated c-Jun expression, and significantly increased cell proliferation and colony formation capability. AGAP3 expression did not have a concordant association with patient prognosis among datasets. Conclusion: CRAG may contribute to development of CRC via activator protein 1 activation.