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

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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.

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Author notes

  1. Han Lian and Baohua Wang contributed to this work equally as co-first authors.

Authors and Affiliations

  1. Department of Neurology, Jingmen No. 1 People’s Hospital, No. 168, Xiangshan Avenue, Duodao District, Jingmen, 448000, Hubei, China

    Han Lian, Baohua Wang, Quan Lu, Bin Chen & Hui Yang

Authors
  1. Han Lian
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  2. Baohua Wang
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  3. Quan Lu
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  4. Bin Chen
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  5. Hui Yang
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Contributions

HL and BW participated in the design of the work, methodology, data interpretation, and drafted the manuscript. QL participated in the collection of data and analysis for the work, carried out the statistical analysis. BC participated in the methodology, data interpretation. Hui Yang participated in data interpretation and methodology.

Corresponding author

Correspondence to Hui Yang.

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Conflict of interest

There is no conflict of interest between authors. Han Lian, Baohua Wang, Quan Lu, Bin Chen and Hui Yang declare that they have no conflict of interest.

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13258_2021_1084_MOESM1_ESM.tif

Figure S1 Downregulation of miR-7-5p abrogated the effects of LINC00943 knockdown on cell viability, apoptosis, and the inflammatory response in MPP+-inducted SK-N-SH cells. SK-N-SH cells were treated with MPP++si-NC, MPP++si-LINC00943, MPP++si-LINC00943 + inhibitor NC, and MPP++si-LINC00943 + miR-7-5p inhibitor. (A) Cell viability was detected by MTT assay in treated SK-N-SH cells. (B) Apoptosis rate was analyzed by flow cytometry assay in treated SK-N-SH cells. (C and D) Protein levels of IL-1β and TNF-α were monitored by western blot assays in treated SK-N-SH cells. (E and F) The ROS generation and SOD activity were evaluated by the corresponding kits in treated SK-N-SH cells. (ANOVA with Tukey’s tests). N = 3, *P < 0.05, **P < 0.01, ***P < 0.001

13258_2021_1084_MOESM2_ESM.tif

Figure S2 MiR-7-5p upregulation promoted cell viability, and repressed apoptosis and inflammatory response by regulating CXCL12 in MPP+-inducted SK-N-SH cells. SK-N-SH cells were treated with MPP++miRNA NC, MPP++miR-7-5p mimic, MPP++miR-7-5p mimic + pc-NC, and MPP++miR-7-5p mimic + pc-CXCL12. (A) Cell viability of treated SK-N-SH cells was detected. (B) The apoptosis rate of treated SK-N-SH cells was examined. (C and D) Protein levels of IL-1β and TNF-α in treated SK-N-SH cells were determined. (E and F) ROS generation and SOD activity of treated SK-N-SH cells were analyzed. (ANOVA with Tukey’s tests). N = 3, *P < 0.05, **P < 0.01

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Lian, H., Wang, B., Lu, Q. et al. LINC00943 knockdown exerts neuroprotective effects in Parkinson’s disease through regulates CXCL12 expression by sponging miR-7-5p. Genes Genom 43, 797–805 (2021). https://doi.org/10.1007/s13258-021-01084-1

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