miR‐302a‐3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia–reoxygenation injury

New Findings What is the central question of this study? How does miR‐302a‐3p play a role in hypoxia–reoxygenation‐induced pyroptosis of renal tubular epithelial cells? What is the main finding and its importance? Hypoxia–reoxygenation treatment upregulated the expression of miR‐302a‐3p in HK‐2 cells, and then inhibited the transcription of FMRP translational regulator 1 (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate the pyroptosis of HK‐2 cells. miR‐302a‐3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure. Abstract Hypoxia–reoxygenation (H/R) induction can affect miRNA expression and then control NLR family pyrin domain containing 3 (NLRP3) inflammasome‐mediated pyroptosis. This study investigated the mechanism of miR‐302a‐3p in H/R‐induced renal tubular epithelial cell (RTEC) pyroptosis. Human HK‐2 RTECs were induced by H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of NLRP3, GSDMD‐N, caspase‐1, interleukin (IL)‐1β, IL‐18, superoxide dismutase, and malondialdehyde were detected to verify the effect of H/R on HK‐2 cells. The NLRP3 inflammasome action was evaluated after H/R‐induced HK‐2 cells were treated with BAY11‐7082, an inflammasome inhibitor. After inhibiting miR‐302a‐3p expression, the changes of pyroptosis were observed. The binding relation between miR‐302a‐3p and FMRP translational regulator 1 (FMR1) was verified. A function‐rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R‐induced HK‐2 cells showed significant pyroptosis injury, and the NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, H/R‐induced apoptosis was inhibited. After H/R treatment, miR‐302a‐3p in HK‐2 cells was increased, and miR‐302a‐3p downregulation limited H/R‐induced NLRP3 inflammasome‐mediated pyroptosis. FMR1 is the target of miR‐302a‐3p. Inhibition of FMR1 alleviated the inhibition of H/R‐induced HK‐2 cell pyroptosis by miR‐302a‐3p inhibitor. Collectively, inhibiting miR‐302a‐3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasomes and reducing caspase‐1‐dependent pyroptosis in HK‐2 cells.