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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

In silico Analysis of Single Nucleotide Polymorphisms Associated with MicroRNA Regulating 5-fluorouracil Resistance in Colorectal Cancer

Author(s): Seyed Hamid Moosavy, Shabnaz Koochakkhani, Mahdi Barazesh, Shiva Mohammadi, Khadijeh Ahmadi, Behnaz Rahnama Inchehsablagh, Soudabeh Kavousipour*, Ebrahim Eftekhar* and Pooneh Mokaram

Volume 19, Issue 2, 2022

Published on: 30 September, 2021

Page: [144 - 159] Pages: 16

DOI: 10.2174/1570180818666210930161618

Price: $65

Abstract

Background: Due to the broad influence and reversible nature of microRNA (miRNA) on the expression and regulation of target genes, researchers suggest that miRNAs and single nucleotide polymorphisms (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 directly or indirectly through regulation of 5-FU chemoresistance in CRC were screened out by 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 SNPs 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 were more critical than other SNPs. Has-miR-320a-5p with 4 SNP in seed region was miRNA with the most number of SNPs. 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 the 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.

Keywords: 5-fluorouracil, colorectal cancer, single nucleotide polymorphisms, microRNA, chemoresistance, ECM-receptor.

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