Effect of statins on lipid metabolism-related microRNA expression in HepG2 cells
| Autor: | Tomás Zambrano, Rosario Dominguez Crespo Hirata, Luis A. Salazar, Raul Hernandes Bortolin, Mario Hiroyuki Hirata, Víctor Manríquez, Alvaro Cerda, Cristina Moreno Fajardo |
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| Rok vydání: | 2020 |
| Předmět: |
Simvastatin
Lipid Metabolism Disorder Atorvastatin Hypercholesterolemia Down-Regulation Biology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor microRNA medicine ESTATINAS Humans cardiovascular diseases RNA Messenger Pharmacology Anticholesteremic Agents nutritional and metabolic diseases Lipid metabolism Cell Differentiation General Medicine Hep G2 Cells Lipid Metabolism LRP1 Up-Regulation MicroRNAs Liver 030220 oncology & carcinogenesis Lipogenesis Cancer research lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2299-5684 |
| Popis: | Statins are potent cholesterol-lowering drugs that prevent cardiovascular events. microRNAs (miRNAs) modulate the expression of genes involved in metabolic pathways and cardiovascular functions post-transcriptionally. This study explored the effects of statins on the expression of miRNAs and their target genes involved in lipid metabolism in HepG2 cells. HepG2 cells were treated with atorvastatin or simvastatin (0.1–10 µM) for 24 h. The expression of 84 miRNAs and nine target genes, selected by in silico studies, was measured by qPCR Array and TaqMan-qPCR, respectively. Five miRNAs were upregulated (miR-129, miR-143, miR-205, miR-381 and miR-495) and two downregulated (miR-29b and miR-33a) in atorvastatin-treated HepG2 cells. Simvastatin also downregulated miR-33a expression. Both statins upregulated LDLR, HMGCR, LRP1, and ABCG1, and downregulated FDFT1 and ABCB1, whereas only atorvastatin increased SCAP mRNA levels. In silico analysis of miRNA–mRNA interactions revealed a single network with six miRNAs modulating genes involved in lipogenesis and lipid metabolism. The statin-dysregulated miRNAs were predicted to target genes involved in cellular development and differentiation, regulation of metabolic process and expression of genes involved in inflammation, and lipid metabolism disorders contributing to metabolic and liver diseases. Atorvastatin-mediated miR-129, miR-143, miR-205, miR-381, and miR-495 upregulation, and miR-29b, and miR-33a downregulation, modulate the expression of target genes involved in lipogenesis and lipid metabolism. Thus, statins may prevent hepatic lipid accumulation and ameliorate dyslipidemia. |
| Databáze: | OpenAIRE |
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