Long non-coding RNA NORAD functions as a microRNA-204-5p sponge to repress the progression of Parkinson's disease in vitro by increasing the solute carrier family 5 member 3 expression

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Long non-coding RNAs have important regulatory values in various human diseases. Non-coding RNA Activated by DNA Damage (NORAD) was reported to regulate PD progression in vitro, but its functional mechanism is fully unknown. We used 1-methyl-4-phenylpyridinium (MPP+) to establish the cell-based PD model. NORAD, microRNA-204-5p (miR-204-5p), and solute carrier family 5 member 3 (SLC5A3) levels were quantified using the quantitative real-time polymerase chain reaction. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry, respectively. The protein levels were analyzed via western blot. Cytotoxicity was assessed by the released lactate dehydrogenase level in cell supernatant. Oxidative stress and inflammation were measured by the standard indicators. Dual-luciferase reporter and RNA immunoprecipitation assays were performed for intergenic combination. First, we found that NORAD was obviously reduced in MPP+-treated neuroblastoma cells and lightened the MPP+-induced cytotoxicity, oxidative stress, and inflammatory response. Then, NORAD was shown to be a miR-204-5p sponge and avoided the injury induced by MPP+ in neuroblastoma cells via targeting miR-204-5p. SLC5A3 was a miR-204-5p target and could be regulated by NORAD/miR-204-5p axis. SLC5A3 knockdown assuaged the anti-miR-204-5p-induced protection for neuroblastoma cells from MPP+. Altogether, NORAD played a neuroprotective role against the progression of MPP+-induced PD model in neuroblastoma cells relying on the miR-204-5p/SLC5A3 axis. This study afforded the clear elaboration on the PD pathomechanism concerning NORAD.