MiR-22-3p modulated the antioxidant activity of curcumin via targeting the cardiolipin synthase gene CRLS1 in LO2 cells

[Display omitted] •Curcumin enhanced cellular antioxidant capacity via downregulating miR-22-3p.•miR-22-3p reduced cellular antioxidant capacity via inhibiting CRLS1 expression.•The redox regulation of miR-22-3p/CRLS1 was attributed to mitochondrial modulation. The antioxidant activity of curcumin has been extensively investigated for years. However, its molecular function mechanism remained unclear. Our preliminary study showed that curcumin downregulated miR-22-3p expression. This study aimed to address whether miR-22-3p mediated the antioxidant activity of curcumin and the possible action mechanism. The results showed that miR-22-3p repression increased the total cellular antioxidant capacity and enhanced the endogenous antioxidant enzyme system of LO2 cells. In addition, miR-22-3p-deteriorated cellular antioxidant capacity was prevented by curcumin pretreatment. Moreover, miR-22-3p inhibition significantly improved mitochondrial function and biogenesis. Further investigation demonstrated that a mitochondrial key regulator, the cardiolipin synthase gene (CRLS1), was targeted and downregulated by miR-22-3p. CRLS1 overexpression also significantly improved cellular antioxidant capacity and enhanced mitochondrial function and biogenesis in LO2 cells. Taken together, all these data suggested that miR-22-3p modulated the antioxidant effect of curcumin via targeting CRLS1, which may provide novel insights into miRNA-mediated antioxidant mechanism of curcumin.