Long Noncoding RNA SNHG12 Regulates Ischemia/reperfusion (I/R)-mediated Acute Kidney Injury (AKI) Through miR-129-1-3p/Ubiquitin Specific Peptidase 25 axis

A growing body of evidence suggests the involvement of long noncoding ribose nucleic acids (lncRNAs) in acute kidney injury (AKI). This study focused on the mechanistic role of lncRNA small nucleolar RNA host gene 12 (SNHG12) in ischemia/reperfusion (I/R)-mediated AKI. A model of hypoxia/reoxygenation (H/R) was created using human kidney cells (HK-2). Expression levels of SNHG12 and miR-129-1-3p mRNAs, and USP25 protein were determined through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting analyses, respectively. Furthermore, the relationship between SNHG12 and miR-129-1-3p, as well as miR-129-1-3p and Ubiquitin Specific Peptidase 25 (USP25), was investigated using dual-luciferase reporter gene, RNA pull-down, and immunoprecipitation assays. To further evaluate the role of SNHG12 in AKI, a mouse model was established to study the pathological changes in kidney tissues after SNHG12 knockdown. SNHG12 was upregulated in H/R-induced HK-2 cells and I/R-induced AKI mouse model. Conversely, the expression of miR-129-1-3p showed a significant downregulation. Through dual-luciferase assay and RNA pull-down analysis, it was demonstrated that SNHG12 interacted with miR-129-1-3p, and miR-129-1-3p acted as a negative regulator of USP25. Silencing SNHG12 attenuated the detrimental effect of H/R on HK-2 cells, which was counteracted by miR-129-1-3p antagomir. USP25 overexpression also reversed the effect of miR-129-1-3p on H/R-induced HK-2 cells. SNHG12 knockdown was further found to ameliorate I/R-induced renal injury, apoptosis, oxidative stress, and inflammation in AKI mouse model. SNHG12 was upregulated in I/R-induced AKI and its knockdown ameliorated AKI through the miR-129-1-3p/USP25 axis. SNHG12/miR-129-1-3p/USP25 axis serves as a potential therapeutic target for I/R-related renal injury.