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

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.

From Genomics to Omics Landscapes of Parkinson's Disease: Revealing the Molecular Mechanisms

“…Long noncoding RNA (lncRNA) and miRNA, a type of short ncRNAs, interfere in transcriptional and translational processes, thus modulating gene expression. Several studies have already investigated ncRNAs and their impact on PD risk in different types of samples (Botta-Orfila et al, 2014 ; Briggs et al, 2015 ; Ding et al, 2016 ; Gui et al, 2015 ; Kraus et al, 2016 ; Margis and Rieder, 2011 ; Martins et al, 2011 ; Minones-Moyano et al, 2011 ; Ni et al, 2017 ; Yilmaz et al, 2016 ). The characteristics of the retrieved studies are presented in Table 3 and in Supplementary Table S5 .…”

Integrated analysis of exosomal lncRNA and mRNA expression profiles reveals the involvement of lnc‐MKRN2‐42:1 in the pathogenesis of Parkinson's disease

“…Recent studies have shown that lncRNAs are closely related to the pathogenesis of PD. High‐throughput gene chip and sequencing screening results showed that a large number of lncRNAs are differentially expressed in brain tissues and peripheral blood of PD patients, PD animals, and cell models of PD, suggesting that lncRNAs are involved in the occurrence of PD. Abnormal expression of lncRNAs was observed in the early stages of PD .…”

Retracted Article: Long noncoding RNA HOTAIR promotes cell apoptosis by sponging miR-221 in Parkinson's disease

“…4 Moreover, lncRNAs play essential roles in regulating cell viability, mitochondrial function and tyrosine hydroxylase (TH) secretion in the SH-SY5Y cells. 5 For example, lncRNA small nucleolar RNA host gene 1 (SNHG1) contributes to 1-methyl-4-phenylpyridine (MPP + )-induced cytotoxicity in PD by regulating cell viability, apoptosis and reactive oxygen species (ROS) production in the SH-SY5Y cells. 6 LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) regulates cell viability and autophagy in MPP +treated SH-SY5Y cells or 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-treated mice by mediating phosphatase and tensin homolog-induced putative kinase 1 (PINK1).…”