Basic & Clinical Cancer Research 2018. 10(2):25-32.

Up-regulation of Bax-interacting factor-1 in Iranian Colorectal Cancer Patients
Elaheh Eskandari, Mahdieh Salimi, Frouzandeh Mahjoubi


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.


Colorectal cancer; Bax-interacting factor-1 (Bif-1); up regulation; Biomarker

Full Text:



Yang J, Du XL, Li S, et al.The risk and survival outcome of subsequent primary colorectal cancer after the first primary colorectal cancer: cases from 1973 to 2012. BMC Cancer. 2017;17:783.

Ko YH, Cho YS, Won HS, et al. Stage-stratified analysis of prognostic significance of Bax-interacting factor-1 expression in resected colorectal cancer. Biomed Res Int. 2013; 2013:329839.

Takahashi Y, Tsotakos N, Liu Y, et al. The Bif-1-Dynamin 2 membrane fission machinery regulates Atg9-containing vesicle generation at the Rab11-positive reservoirs. Oncotarget. 2016; 7:20855-68.

Coppola D, Khalil F, Eschrich S, Boulware D, Yeatman T, Wang HG. Down Regulation of Bax-Interacting Factor-1 (Bif-1) in Colorectal adenocarcinoma. Cancer. 2008;113: 2665–2670.

Runkle KB, Meyerkord CL, Desai NV, Takahashi Y, Wang HG. Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation. Cancer Biol Ther. 2012;13:956-66.

Coppola D, Oliveri C, Sayegh Z, et al. Bax-interacting factor-1 expression in prostate cancer. Clin Genitourin Cancer. 2008; 6:117-21.

Liu Y, Takahashi Y, Desai N, et al. Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance. Sci Rep. 2016; 6:20453.

Wang DB, Kinoshita Y, Kinoshita C, et al. Loss of endophilin-B1 exacerbates Alzheimer's disease pathology. Brain 2015;138:2005-19.

Takahashi Y, Hori T, Cooper TK, et al. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood. 2013;121:1622-32.

Lee JW, Jeong EG, Soung YH, et al. Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas. Pathology.2006; 38:312-5.

Xu L, Wang Z, He SY, et al. Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells. Oncol Rep 2016; 36:3513-3521.

Kim SY, Oh YL, Kim KM, et al. Decreased expression of Bax-interacting factor-1 (Bif-1) in invasive urinary bladder and gallbladder cancers. Pathology. 2008; 40:553-7.

Coppola D, Helm J, Ghayouri M, Malafa MP, Wang HG. Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. Pancreas.2011; 40:433-7.

Gil J, Ramsey D, Szmida E, et al. The BAX gene as a candidate for negative autophagy-related genes regulator on mRNA levels in colorectal cancer. Med Oncol. 2017; 34:16.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25:402–8.

Takahashi Y, Coppola D, Matsushita N, et al., Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nature Cell Biology. 2007; 9: 1142–1151.

Ho J, Kong JW, Choong LY, et al. Novel breast cancer metastasis-associated proteins. J Proteome Res. 2009; 8:583-94.

Fan R, Miao Y, Shan X, et al. Bif-1 is overexpressed in hepatocellular carcinoma and correlates with shortened patient survival. Oncol Lett. 2012; 3: 851-854.

Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013; 368:651–62.

White EJ, Martin V, Liu JL, et al. Autophagy regulation in cancer development and therapy. Am J Cancer Res. 2011; 1:362–72.

Marx J. Autophagy: is it cancer's friend or foe? Science. 2006; 312:1160-1.

Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402:672-6.

Takahashi Y, Meyerkord CL, Hori T, et al., Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy, Autophagy. 2011; 7: 61–73.

Mathew R, Karantza-Wadsworth V, White E. Assessing metabolic stress and autophagy status in epithelial tumors. Methods Enzymol. 2009; 453:53-81.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.