Long non-coding RNA cancer susceptibility candidate 2 (CASC2) alleviates the high glucose-induced injury of CIHP-1 cells via regulating miR-9-5p/PPARγ axis in diabetes nephropathy

Abstract

Background High glucose (HG) induced podocytes injury plays an important role in diabetes nephropathy (DN) development. Long noncoding RNA cancer susceptibility candidate 2 (CASC2) was found to be decreased in serum of DN patients. We aimed to explore the function and possible mechanism of CASC2 in HG induced podocytes injury. Methods Under normal glucose (NG), HG and mannitol stimulated podocyte conditions, the levels of CASC2, microRNA-9-5p (miR-9-5p) and peroxisome proliferator-activated receptor gamma (PPARγ) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Podocyte injury was evaluated by measuring cell viability and apoptosis of CIHP-1 cells were checked by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot was used to detect all protein levels. Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm the relationship between CASC2 and miR-9-5p. Results HG stimulation inhibited the expression levels of CASC2 and PPARγ, but promoted the expression of miR-9-5p. HG could restrain cell viability, autophagy and facilitate apoptosis in CIHP-1 cells, while CASC2 overexpression could reverse HG-induced podocytes injury. Furthermore, CASC2 could be used as a ceRNA to adsorb miR-9-5p, and miR-9-5p mimic overturned the effects of CASC2 on cell viability, autophagy and apoptosis in HG-stimulated podocytes. Additionally, PPARγ was a target gene of miR-9-5p, and CASC2 could weaken the HG-induced podocytes injury by up-regulating PPARγ. Conclusion CASC2 increased cell viability, autophagy and inhibited cell apoptosis by regulating miR-9-5p/PPARγ axis, thus reducing the HG-induced podocytes injury.

Differential Expression of Urinary Exosomal miRNA in Idiopathic Membranous Nephropathy and Evaluation of its Diagnostic Value

“…Both corticosteroid and triptolide can protect podocytes by maintaining miR-30s expression and reducing proteinuria (Wu et al 2014;Yang et al 2017). It has been also found that miR-9-5p can alleviate podocyte injury by being regulated by cancer susceptibility candidate 2 (CASC2) and targeting PPARγ (Li et al 2020). Therefore, miR-30s and miR-9-5p can not only be used as biomarkers of podocytes injury but also play a therapeutic role by regulating their expression.…”

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases

“…Metabolismrelated ceRNA may act as a predictor of the survival outcomes of patients with osteosarcoma (46). CASC2/miR-9-5p/PPARγ alleviates the high glucose-induced cell injury in diabetes nephropathy (47). In polycystic ovary syndrome (PCOS), a ceRNA network is constructed (48), most ceRNA axes are closely related to steroid biosynthesis and metabolic pathways (49), and PWRN2-mediated ceRNA may regulate oocyte nuclear maturation (50).…”

Regulation of Oxidative Stress by Long Non-Coding RNAs in Vascular Complications of Diabetes

“…Cancer susceptibility candidate 2 (CASC2) is located at chromosome 10q26 in humans and was first discovered in 2004 by Baldinu et al [47]. CASC2 acts as a tumor suppressor in various types of cancers [48] and its expression level is reduced in the serum of diabetic nephropathy patients [49], tissues in db/db diabetic mouse, and high glucose-treated human renal mesangial cells [50] and podocyte cells [49][50][51][52]. Upregulation of CASC2 has been shown to attenuate the progression of diabetic nephropathy via various pathways.…”