Plasma long noncoding RNA expression profiles in patients with Parkinson's disease and the role of lnc-CTSD-5:1 in a PD cell model:a ceRNA microarray-based study

REN Zijing; ZHOU Peiyang; TIAN Jing

doi:10.12122/j.issn.1673-4254.2024.11.11

Abstract：Objective To explore the key genes and long non-coding RNAs(lncRNAs)associated with Parkinson's disease(PD).Methods Peripheral blood plasma samples were collected from 6 PD patients and 6 healthy individuals.The mRNA and lncRNA expression profiles were detected using ceRNA microarray technology,and the differentially expressed genes were analyzed using bioinformatics methods.The differentially expressed mRNAs transcribed within 10 kb upstream or downstream of the differentially expressed lncRNAs were defined as potential cis-regulatable(Cis)target genes of the lncRNAs.A PD-specific protein-protein interaction network(PPI)was constructed.Competitive endogenous RNA(ceRNA)networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs.Using MPP+-treated SH-SY5Y cells as a PD cell model,the expressions of the key lncRNAs and their functions were examined.Results We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients(P<0.05).The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis,and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted.Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lnc-MTG2-1:1,lnc-CTSD-5:1,lnc-PCCA-3:1,lnc-VTCN1-3:1,lnc-ZNF25-7:1,and lnc-DAZ3-1:1 might be the key lncRNAs in PD.In MPP+-treated SH-SY5Y cells,the expression of lnc-CTSD-5:1 showed the most significant changes,and silencing lnc-CTSD-5:1 obviously restored the expression level of tyrosine hydroxylase.Conclusion PD patients have significant changes in plasma lncRNA expression profile,and the differentially expressed genes and lncRNAs found in this study may provide new clues for exploring the pathogenesis and identifying potential biomarkers of PD.