Long noncoding RNA LINC00339 promotes renal tubular epithelial pyroptosis by regulating the miR‐22‐3p/NLRP3 axis in calcium oxalate–induced kidney stone

: This study aims to investigate the role of long noncoding RNA (lncRNA) long intergenic nonprotein coding RNA 339 (LINC00339) in regulating renal tubular epithelial pyroptosis in kidney stones and to explore the underlying mechanism. The human renal proximal tubular epithelial (HK-2) cells were treated with calcium oxalate monohydrate (COM) for 72 hours to establish the cell model of renal tubular injury. Relative expression of LINC00339 and miR-22-3p was measured by real-time quantitative reverse transcription polymerase chain reaction. Expression of pyroptosis-related molecules was measured by Western blot analysis (NLRP3, ASC, and cleaved caspase-1 p10) and enzyme-linked immunosorbent assay (interleukin-1β [IL-1β] and IL-18). Pyroptosis was also determined by lactate dehydrogenase release and active caspase-1-propidium iodide double staining. Luciferase reporter assays were performed to verify whether miR-22-3p could bind to LINC00339 or NLRP3. We observed increased LINC00339, decreased miR-22-3p, NLRP3 inflammasome activation, and enhanced cell pyroptosis in COM-treated HK-2 cells. Furthermore, overexpression of both LINC00339 and NLRP3 activated NLRP3 inflammasome and promoted pyroptosis in COM-treated HK-2 cells, whereas miR-22-3p mimic and NLRP3 knockdown exerted the opposite effects. Mechanically, LINC00339 functioned as a competitive endogenous RNA by sponging miR-22-3p to facilitate NLRP3 expression. In conclusion, lncRNA LINC00339 promotes cell pyroptosis by sponging miR-22-3p to regulate NLRP3 expression in COM-treated HK-2 cells.