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

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.