Department of Cardiology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
Cardiovascular Disease Institute, PLA Army General Hospital, Beijing, China.
Biotechnol Lett. 2019 Jul;41(6-7):837-847. doi: 10.1007/s10529-019-02685-3. Epub 2019 May 10.
MiR-499 has been reported to be expressed only in cardiomyocytes, and its expression would increase after acute myocardial infarction (AMI). miR-499 plays a role in the process of cardiomyocytes injury induced by hypoxia/reoxygenation (H/R), however, it still remains unclear.
Hypoxia inhibited miR-499-5p expression and H/R induced apoptosis. SOX6 was a target gene of miR-499-5p, and high expression of miR-499-5p inhibited the expression of SOX6. MiR-499-5p reduced H9c2 cells injury by inhibiting the expression of SOX6, overexpression of which could reverse the effect of miR-499-5p on H9c2 cells. MiR-499-5p inhibited the levels of LDH and MDA, while overexpression of miR-499-5p inhibited H/R-induced cell apoptosis. MiR-499-5p could up-regulate the level of Bcl-2 and down-regulate the expression levels of Bax and caspase-3. However, SOX6 partially reversed these effects of miR-499-5p.
We proved that miR-499-5p inhibited H/R-induced cardiomyocytes injury by targeting SOX6. Our results suggested that miR-499-5p/SOX6 pathway may present a potential therapeutic target for the treatment of AMI.
已有报道称 miR-499 仅在心肌细胞中表达，其表达会在急性心肌梗死（AMI）后增加。miR-499 在缺氧/复氧（H/R）诱导的心肌细胞损伤过程中发挥作用，但具体机制尚不清楚。
缺氧抑制 miR-499-5p 的表达，H/R 诱导细胞凋亡。SOX6 是 miR-499-5p 的靶基因，高表达 miR-499-5p 抑制 SOX6 的表达。miR-499-5p 通过抑制 SOX6 的表达减少 H9c2 细胞损伤，过表达 SOX6 可逆转 miR-499-5p 对 H9c2 细胞的作用。miR-499-5p 降低 LDH 和 MDA 的水平，而过表达 miR-499-5p 抑制 H/R 诱导的细胞凋亡。miR-499-5p 可上调 Bcl-2 的水平，下调 Bax 和 caspase-3 的表达水平。然而，SOX6 部分逆转了 miR-499-5p 的这些作用。
我们证明 miR-499-5p 通过靶向 SOX6 抑制 H/R 诱导的心肌细胞损伤。我们的研究结果表明，miR-499-5p/SOX6 通路可能为 AMI 的治疗提供一个潜在的治疗靶点。
