Up-regulation of Bax-interacting factor-1 in Iranian Colorectal Cancer Patients

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and can be caused by a variety of genetic and acquired/environmental factors. Bax-interacting factor-1 (Bif-1) is an apoptosis inducer gene that interacts with the Bcl2 protein family and triggers apoptosis via direct contact or by changing into the Bax protein conformation using the phosphorylation mechanism. Bif-1 also interacts with Beclin-1, a protein that plays a central role in autophagy through mediation of UVRAG (ultraviolet irradiation resistant-associated gene), a positive regulator of phosphatidylinositol 3-kinase complex 3 (PI3KC3), thereby inducing autophagy in mammalian cells. Considering the dual role of Bif-1 in many tumors of different origins, in this study we assessed Bif-1 gene expression to investigate its potential role as a possible prognostic biomarker in Iranian colorectal cancer patients. Methods: Bif-1 gene expression in tumors and normal adjacent tissues in 50 colorectal cancer patients were quantified using Real-time RT-PCR. Also, the association between Bif-1 gene expression levels with the histopathological characteristics of patients was assessed. Results: The results indicated an overall upregulation of the Bif-1 gene in colorectal tumors compared with normal adjacent tissues (p < 0.0001). Also, Bif-1expression was significantly elevated in stages II and III compared with stage I, and down-regulated in stage IV patients with distant metastasis. A positive association was also observed between lymph node involvement and tumor size ≥ 5 centimeters with Bif-1 overexpression (P < 0.001). Conclusion: In conclusion, up-regulation of the Bif-1 gene could be considered as a possible prognostic candidate in colorectal cancers associated with nodal metastasis and greater tumor size. Further validation of these results are recommended in studies with larger sample sizes.