Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Laboratory of Molecular Research in Cardiology, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil.
Epigenomics. 2021 May;13(10):779-791. doi: 10.2217/epi-2020-0462. Epub 2021 Apr 26.
Functional analysis of 3'UTR variants and mRNA-miRNA interactions were explored in patients with familial hypercholesterolemia (FH). 3'UTR variants were identified by exon-targeted gene sequencing. Functional effects of 3'UTR variants and mRNA-miRNA interactions were analyzed using and studies in HEK293FT and HepG2 cells. Twelve 3'UTR variants were detected in 88 FH patients. c.*75C >T and c.*345C >T disrupted interactions with miR-6875, miR-4721 and miR-564. Transient transfection of the c.*345C >T decreased luciferase activity in HEK293FT cells. miR-4721 and miR-564 mimics reduced expression in HepG2 cells. c.*345C >T has a possible role as loss-of-function variant. miR-4721 and miR-564 downregulate and may be useful to improve lipid profile in FH patients.
对家族性高胆固醇血症 (FH) 患者的 3'UTR 变异体和 mRNA-miRNA 相互作用进行功能分析。通过外显子靶向基因测序鉴定 3'UTR 变异体。在 HEK293FT 和 HepG2 细胞中使用 和 研究分析 3'UTR 变异体和 mRNA-miRNA 相互作用的功能效应。在 88 名 FH 患者中检测到 12 个 3'UTR 变异体。c.*75C>T 和 c.*345C>T 破坏了与 miR-6875、miR-4721 和 miR-564 的相互作用。c.*345C>T 的瞬时转染降低了 HEK293FT 细胞中的荧光素酶活性。miR-4721 和 miR-564 模拟物降低了 HepG2 细胞中的 表达。c.*345C>T 可能作为功能丧失变异体发挥作用。miR-4721 和 miR-564 下调 ，可能有助于改善 FH 患者的血脂谱。
