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Functional Analysis of PCSK9 3′UTR Variants and mRNA–miRNA Interactions in Patients with Familial Hypercholesterolemia

2021; Future Medicine; Volume: 13; Issue: 10 Linguagem: Inglês

10.2217/epi-2020-0462

1750-1911

Bruna Los, Jéssica Bassani Borges, Victor Fernandes de Oliveira, Renata Caroline Costa de Freitas, Carolina Dagli-Hernandez, Raul Hernandes Bortolin, Rodrigo Marques Gonçalves, André Árpád Faludi, Alice Cristina Rodrigues, Gisele Medeiros Bastos, Cinthia Elim Jannes, Alexandre C. Pereira, Rosário Dominguez Crespo Hirata, Mário Hiroyuki Hirata,

Genetic factors in colorectal cancer

Aim: Functional analysis of PCSK9 3′UTR variants and mRNA–miRNA interactions were explored in patients with familial hypercholesterolemia (FH). Materials & methods: PCSK9 3′UTR variants were identified by exon-targeted gene sequencing. Functional effects of 3′UTR variants and mRNA–miRNA interactions were analyzed using in silico and in vitro studies in HEK293FT and HepG2 cells. Results: Twelve PCSK9 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 PCSK9 expression in HepG2 cells. Conclusion: PCSK9 c.*345C >T has a possible role as loss-of-function variant. miR-4721 and miR-564 downregulate PCSK9 and may be useful to improve lipid profile in FH patients.