Department of Basic Sciences, Center of Excellence in Translational Medicine, BIOREN, Universidad de La Frontera, Av. Alemania 0458, 4810296, Temuco, Chile.
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Pharmacol Rep. 2021 Jun;73(3):868-880. doi: 10.1007/s43440-021-00241-3. Epub 2021 Mar 15.
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.
他汀类药物是强效的降胆固醇药物，可预防心血管事件。微小 RNA（miRNA）在后转录水平上调节参与代谢途径和心血管功能的基因的表达。本研究探讨了他汀类药物对 HepG2 细胞中脂质代谢相关 miRNA 及其靶基因表达的影响。
用阿托伐他汀或辛伐他汀（0.1-10 μM）处理 HepG2 细胞 24 h。用 qPCR 芯片和 TaqMan-qPCR 分别检测 84 个 miRNA 和 9 个靶基因的表达，这些基因是通过计算机预测选择的。
阿托伐他汀处理的 HepG2 细胞中有 5 个 miRNA 上调（miR-129、miR-143、miR-205、miR-381 和 miR-495），2 个下调（miR-29b 和 miR-33a）。辛伐他汀也下调了 miR-33a 的表达。两种他汀类药物均上调了 LDLR、HMGCR、LRP1 和 ABCG1，下调了 FDFT1 和 ABCB1，而只有阿托伐他汀增加了 SCAP mRNA 水平。miRNA-mRNA 相互作用的计算机分析显示，仅有一个网络存在，其中 6 个 miRNA 调节参与脂肪生成和脂质代谢的基因。他汀类药物失调的 miRNA 被预测靶向参与细胞发育和分化、代谢过程调节以及炎症相关基因表达和脂质代谢紊乱的基因。
阿托伐他汀介导的 miR-129、miR-143、miR-205、miR-381 和 miR-495 上调，以及 miR-29b 和 miR-33a 下调，调节参与脂肪生成和脂质代谢的靶基因的表达。因此，他汀类药物可能预防肝脏脂质堆积并改善血脂异常。
