Identification of a new deleterious single nucleotide polymorphism related to CDKN3 gene in colorectal cancer by bioinformatics analysis
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sajede naghiyan fesharaki,1,* Sajjad Sisakhtnezhad,2
1. Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
2. Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
- Introduction: Introduction: Colorectal cancer (CRC) is the third most popular occurring cancer in men and the second most commonly occurring cancer in women. It is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract. CRC is more likely to be due to old age and lifestyle factors, and a small number of people become infected due to mutations in intestinal crypt stem cells [1]. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue. It typically starts as a benign tumor [2]. CDKN3 gene is located position on chromosome 14q22.2 and contains 9 exons. Different studies indicated that this gene is associated with CRC. Cyclin-dependent kinase inhibitor 3 (CDKN3) is a member of the protein kinase family with Krüppel-associated box repression domains that have synergistic and inhibitory effects on zinc finger proteins. CDKN3 plays a dual role in cell cycle control, either blocking or promoting cell cycle progression in specific tumors or tumor stages [3]. Single nucleotide polymorphism (SNPs) are consisting genetic marker related to many of the genetic diseases that variation at a single position in a DNA sequence among individuals that this particular alteration is made in at least 1% of the population [4]. Given the importance of SNPs as biological markers of cancer, this study aimed to investigate new deleterious SNPs related to CDKN3 gene in CRC by bioinformatics analysis.
- Methods: Methods: In this study, NCBI, PROVEAN, SIFT, and HOPE online bioinformatics webservers were used for evaluation of new deleterious SNPs in CDKN3 gene and their effects of its protein in CRC.
- Results: Results: We detected several SNPs in the protein coding region of CDKN3 gene. From all of the extracted SNPs, rs78293998 introduced as the most significant deleterious SNP in the protein-coding region of CDKN3 gene. Our bioinformatics analysis indicated that rs78293998 is associated to the substitution of the reference (wild) A allele with the alternative (mutant) G allele in the CDKN3 gene. Based on the biophysical validation of HOPE, this SNP is cause the arginine mutation into Isoleucine at the 72nd position of CDKN3 protein. The wild-type and mutant amino acids differ in size. Also, the mutant residue is smaller and this might lead to loss of interactions, therefore this mutation is probably damaging to the protein
- Conclusion: Conclusion: In general, we conclude that rs78293998 is associated with CDKN3 gene and CRC. Moreover, the formation of rs78293998 may increase the incidence of CRC by changing the structure of the CDKN3 protein. However, experimental studies are needed to validate the result of this in silico study.
- Keywords: Keywords: Colorectal cancer, CDKN3 gene, SNPs, Bioinformatics analysis, rs78293998
