Tags

Type your tag names separated by a space and hit enter

LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression.
Aging (Albany NY). 2021 01 20; 13(3):4115-4137.A

Abstract

In vitro and in vivo models of Parkinson's disease were established to investigate the effects of the lncRNA XIST/miR-199a-3p/Sp1/LRRK2 axis. The binding between XIST and miR-199a-3p as well as miR-199a-3p and Sp1 were examined by luciferase reporter assay and confirmed by RNA immunoprecipitation analysis. Following the Parkinson's disease animal behavioural assessment by suspension and swim tests, the brain tissue injuries were evaluated by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labelling, and tyrosine hydroxylase stainings. The results indicated that miR-199a-3p expression was downregulated, whereas that of XIST, Sp1 and LRRK2 were upregulated in Parkinson's disease. Moreover, miR-199a-3p overexpression or XIST knockdown inhibited the cell apoptosis induced by MPP+ treatment and promoted cell proliferation. The neurodegenerative defects were significantly recovered by treating the cells with shXIST or shSp1, whereas miR-199a-3p inhibition or Sp1 and LRRK2 overexpression abrogated these beneficial effects. Furthermore, the results of our in vivo experiments confirmed the neuroprotective effects of shXIST and miR-199a-3p against MPTP-induced brain injuries, and the Parkinson's disease behavioural symptoms were effectively alleviated upon shXIST or miR-199a-3p treatment. In summary, the results of the present study showed that lncRNA XIST sponges miR-199a-3p to modulate Sp1 expression and further accelerates Parkinson's disease progression by targeting LRRK2.

Links

Authors+Show Affiliations

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33494069

Citation

Zhou, Qian, et al. "LncRNA XIST Sponges miR-199a-3p to Modulate the Sp1/LRRK2 Signal Pathway to Accelerate Parkinson's Disease Progression." Aging, vol. 13, no. 3, 2021, pp. 4115-4137.

Zhou Q, Zhang MM, Liu M, et al. LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression. Aging (Albany NY). 2021;13(3):4115-4137.

Zhou, Q., Zhang, M. M., Liu, M., Tan, Z. G., Qin, Q. L., & Jiang, Y. G. (2021). LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression. Aging, 13(3), 4115-4137. https://doi.org/10.18632/aging.202378

Zhou Q, et al. LncRNA XIST Sponges miR-199a-3p to Modulate the Sp1/LRRK2 Signal Pathway to Accelerate Parkinson's Disease Progression. Aging (Albany NY). 2021 01 20;13(3):4115-4137. PubMed PMID: 33494069.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression. AU - Zhou,Qian, AU - Zhang,Ming-Ming, AU - Liu,Min, AU - Tan,Zhi-Gang, AU - Qin,Qi-Lin, AU - Jiang,Yu-Gang, Y1 - 2021/01/20/ PY - 2019/12/11/received PY - 2020/09/14/accepted PY - 2021/1/26/pubmed PY - 2021/8/17/medline PY - 2021/1/25/entrez KW - LRRK2 KW - Parkinson's disease KW - Sp1 KW - lncRNA XIST KW - miR-199a-3p SP - 4115 EP - 4137 JF - Aging JO - Aging (Albany NY) VL - 13 IS - 3 N2 - In vitro and in vivo models of Parkinson's disease were established to investigate the effects of the lncRNA XIST/miR-199a-3p/Sp1/LRRK2 axis. The binding between XIST and miR-199a-3p as well as miR-199a-3p and Sp1 were examined by luciferase reporter assay and confirmed by RNA immunoprecipitation analysis. Following the Parkinson's disease animal behavioural assessment by suspension and swim tests, the brain tissue injuries were evaluated by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labelling, and tyrosine hydroxylase stainings. The results indicated that miR-199a-3p expression was downregulated, whereas that of XIST, Sp1 and LRRK2 were upregulated in Parkinson's disease. Moreover, miR-199a-3p overexpression or XIST knockdown inhibited the cell apoptosis induced by MPP+ treatment and promoted cell proliferation. The neurodegenerative defects were significantly recovered by treating the cells with shXIST or shSp1, whereas miR-199a-3p inhibition or Sp1 and LRRK2 overexpression abrogated these beneficial effects. Furthermore, the results of our in vivo experiments confirmed the neuroprotective effects of shXIST and miR-199a-3p against MPTP-induced brain injuries, and the Parkinson's disease behavioural symptoms were effectively alleviated upon shXIST or miR-199a-3p treatment. In summary, the results of the present study showed that lncRNA XIST sponges miR-199a-3p to modulate Sp1 expression and further accelerates Parkinson's disease progression by targeting LRRK2. SN - 1945-4589 UR - https://www.unboundmedicine.com/medline/citation/33494069/LncRNA_XIST_sponges_miR_199a_3p_to_modulate_the_Sp1/LRRK2_signal_pathway_to_accelerate_Parkinson's_disease_progression_ DB - PRIME DP - Unbound Medicine ER -