Circ_0123996 promotes the proliferation, inflammation, and fibrosis of mesangial cells by sponging miR-203a-3p to upregulate SOX6 in diabetic nephropathy.

Circular RNA has been reported to participate in human diseases including diabetic nephropathy (DN). However, the role and mechanism of circ_0123996 in DN need to be further explored. Relative expression levels of circ_0123996, microRNA (miR)-203a-3p, SRY-box 6 (SOX6), and inflammatory cytokines were determined using quantitative real-time PCR. Western blot analysis was used to detect the protein expression of SOX6 and fibrosis-related markers. Cell proliferation was measured using the Cell Counting Kit 8 assay. The interaction between miR-203a-3p and circ_0123996 or SOX6 was verified using the dual-luciferase reporter assay. The circ_0123996 and SOX6 expression were increased and the miR-203a-3p expression was decreased in high glucose-induced mesangial cells. Silenced circ_0123996 could hinder the proliferation, inflammation, and fibrosis of mesangial cells. In terms of mechanism, circ_0123996 could sponge miR-203a-3p to positively regulate SOX6 expression. Function experiments revealed that miR-203a-3p inhibitor could abolish the regulation of circ_0123996 silencing on mesangial cell proliferation, inflammation, and fibrosis. In addition, the knockdown of SOX6 could inhibit mesangial cell proliferation, inflammation, and fibrosis. Also, SOX6 overexpression could reverse the regulation of circ_0123996 silencing on mesangial cell progression. In summary, our data revealed that circ_0123996 promoted the proliferation, inflammation, and fibrosis of mesangial cells via modulating the miR-203a-3p/SOX6 axis, suggesting that circ_0123996 might be a target for alleviating DN progression.