LINC00943 knockdown exerts neuroprotective effects in Parkinson's disease through regulates CXCL12 expression by sponging miR-7-5p

Genes Genomics. 2021 Jul;43(7):797-805. doi: 10.1007/s13258-021-01084-1. Epub 2021 Apr 22.

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative movement disorder, but the pathogenesis is still unclear. Long non-coding RNAs (lncRNAs) have been reported to play a prominent role in PD.

Objective: This study is designed to explore the role and mechanism of long intergenic non-coding RNA 00943 (LINC00943) in the N-methyl-4-phenylpyridine (MPP+)-inducted PD model.

Methods: LINC00943, microRNA-7-5p (miR-7-5p), and the chemokine (C-X-C motif) ligand 12 (CXCL12, also referred to as SDF-1) level were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were analyzed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), and flow cytometry assays, severally. Protein levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and CXCL12 were assessed by western blot assay. The ROS generation and SOD activity were detected by the corresponding kits. The binding relationship between miR-7-5p and LINC00943 or CXCL12 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.

Results: LINC00943 and CXCL12 were increased, and miR-7-5p was decreased in MPP+-inducted SK-N-SH cells. LINC00943 silencing promoted cell viability, and repressed apoptosis and the inflammatory response in MPP+-treated SK-N-SH cells. The mechanical analysis discovered that LINC00943 acted as a sponge of miR-7-5p to regulate CXCL12 expression.

Conclusions: LINC00943 knockdown could attenuate MPP+-triggered neuron injury by regulating the miR-7-5p/CXCL12 axis, hinting at a promising therapeutic target for PD treatment.

Keywords: CXCL12; LINC00943; Parkinson’s disease; miR-7-5p.

MeSH terms

  • 1-Methyl-4-phenylpyridinium
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Chemokine CXCL12 / genetics*
  • Gene Knockdown Techniques*
  • Humans
  • MicroRNAs / metabolism*
  • Neuroprotection / genetics*
  • Neuroprotection / physiology
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Up-Regulation

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • 1-Methyl-4-phenylpyridinium