Rs884225 polymorphism is associated with primary hypertension by compromising interaction between epithelial growth factor receptor (EGFR) and miR‐214
| Autor: | Yiming Yuan, Fang Luo, Weiguo Jia, Yitian Wu, Qunfang Ding |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Untranslated region Genotype EGFR microRNA‐214 Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) microRNA Gene expression Humans 3' Untranslated Regions MEG3 Binding Sites Haplotype apoptosis Original Articles Cell Biology rs884225 Prognosis Molecular biology ErbB Receptors primary hypertension MicroRNAs 030104 developmental biology Gene Expression Regulation Case-Control Studies 030220 oncology & carcinogenesis Molecular Medicine Female RNA Long Noncoding Original Article Essential Hypertension |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.15976 |
| Popis: | Genetic variations in the 3′UTR of mRNAs as well as sequences of microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs) can affect gene expression by interfering with the binding between them. In this study, we investigated the role of the following polymorphisms in the risk of hypertension: the 774T > C (rs17337023) polymorphism located in the EGFR 3’ untranslated region (3’UTR), the rs884225 polymorphism located in the sequence of miR‐214, and the single nucleotide polymorphisms (SNPs) rs325797437, rs344501106, rs81286029 and rs318656749 located in the promoter of lncRNA MEG3. Taqman genotyping assays and haplotype analysis tools were used to measure the MEG3 haplotypes and the rs17337023 and rs884225 polymorphisms genotypes. The relationship between MEG3, miR‐214 and EGFR was validated using computational analysis and luciferase assays. Unlike other polymorphisms, only patients grouped according to their rs884225 genotypes exhibited varied EGFR mRNA and protein levels, which indicated that the rs884225 genotype is associated with the expression of EGFR mRNA and protein levels. MiR‐214 was confirmed to bind to MEG3 and 3’UTR of EGFR by showing that the transfection of exogenous miR‐214 significantly down‐regulated the luciferase activity of A549 and H460 cells transfected with wild‐type MEG3 or wild‐type EGFR 3’ UTR. Additionally, MEG3 overexpression inhibited miR‐214 expression while elevating the EGFR mRNA and protein expressions. Meanwhile, MEG3 down‐regulation demonstrated an opposite result, thus establishing the MEG3/miR‐214/EGRF signalling pathway. Our study confirmed that the T > C substitution of rs884225 polymorphism located in miR‐214 binding site in the 3’UTR of EGFR is associated with increased risk of primary hypertension. |
| Databáze: | OpenAIRE |
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