Investigation of Long Non-coding RNA Expression Profiles in the Substantia Nigra of Parkinson's Disease

Cell Mol Neurobiol. 2017 Mar;37(2):329-338. doi: 10.1007/s10571-016-0373-0. Epub 2016 May 5.

Abstract

Genetics is considered as an important risk factor in the pathological changes of Parkinson's disease (PD). Substantia nigra (SN) is thought to be the most vulnerable area in this process. In recent decades, however, few related long non-coding RNAs (lncRNAs) in the SN of PD patients had been identified and the functions of those lncRNAs had been studied even less. In this study, we sought to investigate the lncRNA expression profiles and their potential functions in the SN of PD patients. We screened lncRNA expression profiles in the SN of PD patients using the lncRNA mining approach from the ArrayExpress database, which included GSE20295. The samples were from 11 of PD and 14 of normal tissue samples. We identified 87 lncRNAs that were altered significantly in the SN during the occurrence of PD. Among these lncRNAs, lncRNA AL049437 and lncRNA AK021630 varied most dramatically. AL049437 was up-regulated in the PD samples, while AK021630 was down-regulated. Based on the results, we focused on the potential roles of the two lncRNAs in the pathogenesis of PD by the knockdown of the expression of AL049437 or AK021630 in human neuroblastoma SH-SY5Y cell line. Results indicated that the reduction in AL049437 level increased cell viability, mitochondrial transmembrane potential (Δψm), mitochondrial mass, and tyrosine hydroxylase (TyrH) secretion. By contrast, the knockdown of AK021630 resulted in the opposite effect. Based on these results, we speculated that lncRNA AL049437 likely contributed to the risk of PD, while lncRNA AK021630 likely inhibited the occurrence of PD.

Keywords: Long non-coding RNA; Parkinson’s disease; Substantia nigra; lncRNA AK021630; lncRNA AL049437.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling / methods*
  • Humans
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics*
  • Rotenone / pharmacology
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology

Substances

  • RNA, Long Noncoding
  • Rotenone