Nephrolithiasis is a clinical entity with long-term course, facing rising global prevalence and recurrence rates. Long noncoding RNAs (LncRNAs) have emerged as regulators implicated in the progression of nephrolithiasis, yet the functional role of lncRNA MIR205HG remains poorly characterized. Our research attempted to investigate the function of the lncRNA MIR205HG in calcium oxalate nephrolithiasis and focus on its in-depth competitive endogenous RNA (ceRNA) regulatory network. MIR205HG expression in the Randall's plaque tissues of calcium oxalate (CaOx) nephrolithiasis patients and calcium oxalate monohydrate (COM)-stimulated HK2 cells was examined with GSE117518 dataset from GEO database and RT-qPCR. CCK-8 and flow cytometry assays separately estimated cell viability and apoptosis. DCFH-DA probe and western blotting measured oxidative stress mediators. RT-qPCR also tested miR-5581-3p and follistatin-like protein 1 (FSTL1) expressions. A targeting relationship among MIR205HG, miR-5581-3p and FSTL1 was determined using bioinformatics software and luciferase reporter assays. Besides, cellular morphology was observed and cell adhesion was detected. Western blotting assessed epithelial-mesenchymal transition (EMT) markers. A total of 62 upregulated and 17 downregulated genes were identified. MIR205HG expression was elevated both in the Randall’s plaque tissues of calcium oxalate (CaOx) nephrolithiasis patients and COM-stimulated HK2 cells. MIR205HG silencing promoted the viability, inhibited the apoptosis, and ameliorated the oxidative stress in COM-induced HK2 cells. MIR205HG could sequester miR-5581-3p which directly targeted FSTL1. In addition to the impacts on FSTL1 expression, cell viability, apoptosis and oxidative stress, miR-5581-3p inhibitor could also restore the suppressive role of MIR205HG knockdown in the morphological changes, EMT and adhesion of COM-induced HK2 cells. Conclusively, lncRNA MIR205HG participated in the process of CaOx nephrolithiasis through mediating the miR-5581-3p/FSTL1 pathway.
Zhou et al. (Thu,) studied this question.