Functional SNP in microRNA‐491‐5p binding site of MMP9 3′‐UTR affects cancer susceptibility
| Autor: | Hossein Sazegar, Niloofar Jafari, Mona Tamadon, Mehrnoosh Fathi-Roudsari, Gelareh Shokri, Fatemeh Kouhkan, Nooshin Tasharrofi, Homeira Javadi Pirooz, Mozhdeh Rastegari |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Genotype MiRNA binding Iran Biology Polymorphism Single Nucleotide Biochemistry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA Gene expression medicine Humans Genetic Predisposition to Disease Binding site 3' Untranslated Regions Molecular Biology Regulation of gene expression Binding Sites Three prime untranslated region Cancer Cell Biology medicine.disease Molecular biology Gene Expression Regulation Neoplastic body regions MicroRNAs 030104 developmental biology Matrix Metalloproteinase 9 030220 oncology & carcinogenesis Female |
| Zdroj: | Journal of Cellular Biochemistry. 119:5126-5134 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.26471 |
| Popis: | MicroRNAs (miRNA) are small RNA molecules that negatively regulate gene expression through base pairing interactions between 3′-UTR of the target mRNAs and seed sequence of miRNA. Any changes in the recognition site could destroy binding sites or modify binding affinity, resulting in evasion from miRNA regulation. A putative binding site for miR-491-5p resides in 3′-UTR of MMP9, and a genetic variant (rs1056628 A→C) is present in this region. The role of MMP9 over expression well marked in various cancers. However, whether rs1056628 SNP in miR-491-5p binding site of MMP9 3′-UTR could abrogate its post-transcriptional regulation and affect cancer susceptibility remains largely unknown. To test this, the rs1056628 SNP was genotyped in 300 cases of lung, gastric and breast cancers and 200 age- and sex-matched healthy controls. The results showed that compared with the AA genotype, C was a risk genotype for all three cancers development and was also associated with gastric and breast cancers metastasis and invasion. Based on the base pairing analysis and secondary structure evaluation of MMP9 mRNA and miR-491-5p, we found that miR-491-5p had a higher binding affinity for A genotype than the C genotype. The Luciferase activity of MMP9 3′-UTR indicates differential regulation of two genetic variations of MMP9. Overexpression of miR-491-5p decreased MMP9 mRNA level in cell lines of gastric, breast and lung cancers and thus leads to decreasing of the invasion ability. Therefore, for the first time we imply that the C variant of MMP9 contributes to the likelihood of gastric, breast and lung cancers susceptibility via a novel mechanism of subtle gene regulation through miRNA binding capacity. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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