LncRNA NEAT1 Regulates the Development of Parkinson’s Disease by Targeting AXIN1 Via Sponging miR-212-3p

• Published in: Neurochemical research 2021-02, Vol.46 (2), p.230-240
• Main Authors: Liu, Tao, Zhang, Yang, Liu, Weihong, Zhao, Jinsheng
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Apoptosis; Apoptosis - physiology; Assaying; Axin Protein - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Cell Line, Tumor; Down-Regulation; Enzyme-linked immunosorbent assay; Flow cytometry; Gene Knockdown Techniques; Humans; Immunoprecipitation; In vivo methods and tests; Inflammation; Inflammation - metabolism; Inhibitors; Mice; Mice, Inbred C57BL; MicroRNAs - metabolism; miRNA; Movement disorders; MPP; MPTP; Neurochemistry; Neurodegenerative diseases; Neurology; Neuroprotection; Neurosciences; Non-coding RNA; Original Paper; Parkinson Disease - metabolism; Parkinson's disease; Polymerase chain reaction; Proteins; Pyridines; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Therapeutic targets; Transcription; Up-Regulation
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-020-03157-1

Long non-coding RNA (lncRNA) nuclear-enriched assembly transcript 1 ( NEAT1 ) has been reported to be highly expressed in Parkinson’s disease (PD). However, the mechanism of NEAT1 in PD progression has not been fully elucidated. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine injection (MPTP) was used to construct PD mouse models in vivo, and 1-methyl-4-phenyl pyridine (MPP + ) was used to build PD cell models in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to test the expression of NEAT1 , microRNA (miR)-212-3p and axis inhibition protein 1 ( AXIN1 ). The viability, apoptosis and inflammation of cells were determined using cell counting kit 8 (CCK8) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Then, the protein levels of apoptosis-related markers and AXIN1 were measured by western blot (WB) analysis. Furthermore, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction between miR-212-3p and NEAT1 or AXIN1 . NEAT1 was upregulated in PD mouse models and cell models. Function experiments confirmed that NEAT1 knockdown could promote the viability, suppress the apoptosis and inflammation of MPP + -stimulated SK-N-SH cells to restrain PD progression. MiR-212-3p was downregulated in PD, and its inhibitor could reverse the suppression effect of NEAT1 knockdown on PD progression. Additionally, AXIN1 was a target of miR-212-3p , and its overexpression could invert the inhibition effect of miR-212-3p mimic on PD progression. Furthermore, AXIN1 expression was inhibited by NEAT1 silencing and promoted by NEAT1 overexpression, while these effect could be recovered by miR-212-3p inhibitor and mimic, respectively. Our results demonstrated that NEAT1 knockdown suppressed PD progression through regulating the miR-212-3p / AXIN1 pathway, indicating that NEAT1 might be a therapeutic target for neuroprotection in PD.