miR-499 通过靶向 SOX6 抑制低氧/复氧诱导的心肌细胞损伤。

MiR-499 inhibited hypoxia/reoxygenation induced cardiomyocytes injury by targeting SOX6.

机构信息

Department of Cardiology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.

Cardiovascular Disease Institute, PLA Army General Hospital, Beijing, China.

出版信息

Biotechnol Lett. 2019 Jul;41(6-7):837-847. doi: 10.1007/s10529-019-02685-3. Epub 2019 May 10.

OBJECTIVE

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.

RESULTS

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.

CONCLUSION

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.

目的

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。

结果

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。