In silico analysis of Single Nucleotide Polymorphisms Associated with MicroRNA Regulating 5-fluorouracil resistance in colorectal cancer

Author:

Moosavy Seyed Hamid1,Koochakkhani Shabnaz1,Barazesh Mahdi2,Mohammadi Shiva3,Ahmadi Khadijeh4,Inchehsablagh Behnaz Rahnama5,Kavousipour Soudabeh6,Eftekhar Ebrahim6,Mokaram Pooneh7

Affiliation:

1. Endocrinology and Metabolism Research Center, Hormozgan University of Medical Science, Bandar Abbas, Iran

2. School of Paramedical Sciences, Gerash University of Medical Sciences, Gerash, Iran

3. Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

4. Infection and tropical disease research center, Hormozgan Health Institute, Hormozgan University of Medical Science, Bandar Abbas, Iran

5. Department of Physiology and Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

6. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran

7. Autophagy research center, Shiraz University of Medical sciences, Iran

Abstract

Background: The broad influence and reversible nature of microRNA (miRNA) on the expression and regulation of target genes lead to research suggest that miRNAs and Single nucleotide (SNPs) in miRNA genes interfere with 5-fluorouracil (5-FU) drug resistance in colorectal cancer chemotherapy. Methods: Computational assessment and cataloging of miRNA gene polymorphisms that target mRNA transcripts straightly or indirectly through regulation of 5-FU chemoresistance in CRC were screened out applying various universally accessible datasets such as miRNA SNP3.0 software. Results: 1255 SNPs in 85 miRNAs affecting 5-FU resistance (retrieved from literature) were detected. Computational analysis showed that 167 from 1255 SNP alter microRNA expression levels leading to inadequate response to 5-FU resistance in CRC. Among these 167 SNPs, 39 were located in the seed region of 25/85 miRNA and are more critical than other SNPs. Has-miR-320a-5p with 4 SNP in seed region was miRNA with the most number of SNP. On the other hand, it has been identified that proteoglycan in cancer, adherents junction, ECM-receptor interaction, Hippo signaling pathway, TGF-beta signaling cascade, biosynthesis of fatty acid, and fatty acid metabolism were the most important pathways targeted by these 85 predicted miRNAs. Conclusion: Our data suggest 39 SNPs in seed region of 25 miRNAs as catalog in miRNA genes that control the 5-FU resistance in CRC. These data also identify the most important pathways regulated by miRNA.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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