The regulatory role of MiR-203 in oxidative stress induced cell injury through the CBS/H2S pathway

Abstract

Hydrogen Sulfide (H₂S) mediates biological effects in a variety of ways. Due to its strong reducing potential, H₂S has been recognized to have an important role in oxidative stress induced hypoxia. It has been reported that H₂S production and miRNA can mutually regulate each other. H₂S is produced by the catalytic activity of cystathionine-β-synthase (CBS), which is under the regulation of miRNAs. In this study, we used target gene prediction software, and identified miR-203 as a potential regulator of CBS. We verified this finding using an oxygen and glucose deprivation (OGD) hypoxia cell model in SH-SY5Y cells and pMIR-REPORT™ luciferase miRNA expression reporter vector. Furthermore, transfecting SH-SY5Y cells with miRNA agomir (agonist) and antagomir (antagonist) by lipofectamin RNAiMAX, we further validated miR-203 as a direct regulator of CBS. We also found that miR-203 protects from cell injury by regulating lipid peroxidation, cell apoptosis, and mitochondrial membrane potential. These findings suggest that while over-expression of miR-203 can aggravate OGD induced cell injury, inhibition of miR-203 can protect against OGD induced cell injury. Based on our data and that of others, we propose that miR-203 may regulate oxidative stress induced cell injury by regulating CBS expression and adjusting the levels of H₂S production.

Keywords: Cerebral infarction; Cystathionine-β-synthase; Hydrogen sulfide; miRNA-203.