Dataset Information

Aberrantly expressed long noncoding RNAs and genes in Parkinson's disease.

ABSTRACT: Purpose:Parkinson's disease (PD) is a common neurodegenerative movement disorder, but the pathogenesis remains elusive. This study was aimed to explore key genes and long noncoding RNAs (lncRNAs) associated with PD. Materials and methods:Three patients with PD and three normal controls were enrolled in the present study from July 12, 2017, to August 29, 2017. RNA sequencing and bioinformatics analysis were performed to obtain differentially expressed micro RNAs (DEmRNAs) and lncRNAs (DElncRNAs) between patients with PD and normal controls. PD-specific protein-protein interaction networks were constructed. DEmRNAs transcribed within a 100 kb window upstream or downstream of DElncRNAs were searched, which were defined as cis nearby targeted DEmRNAs of DElncRNAs. Datasets GSE57475 and GSE68719 were downloaded from the Gene Expression Omnibus database, which were used to validate the expression of selected DEmRNAs. Results:A total of 857 DEmRNAs and 77 DElncRNAs were obtained between PD and normal controls. Natural killer cell-mediated cytotoxicity was a significantly enriched pathway in PD. ERBB2, HSPB1, and MYC were three hub proteins of PD-specific protein-protein interaction network. LOC105378701-TAL1, LOC102724104-CX3CR1, LOC105375056-TREML1/TREML4, LOC105379392-ANK1, and LOC101928100-KLRK1/KLRD1 interactions were identified DElncRNA nearby targeted DEmRNA pairs in PD. Gene expression results validated by GSE57475 and GSE68719 were consistent with our RNA-sequencing results, generally. Conclusion:This present study identified key genes and lncRNAs associated with PD, which will provide new clues for exploring the pathogenesis and developing potential biomarkers of PD.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6257365 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Aberrantly expressed long noncoding RNAs and genes in Parkinson's disease.

Zhou Yong Y Gu Chengzhi C Li Jia J Zhu Lianhai L Huang Guoxiang G Dai Jie J Huang Huaiyu H

Neuropsychiatric disease and treatment 20181122

<h4>Purpose</h4>Parkinson's disease (PD) is a common neurodegenerative movement disorder, but the pathogenesis remains elusive. This study was aimed to explore key genes and long noncoding RNAs (lncRNAs) associated with PD.<h4>Materials and methods</h4>Three patients with PD and three normal controls were enrolled in the present study from July 12, 2017, to August 29, 2017. RNA sequencing and bioinformatics analysis were performed to obtain differentially expressed micro RNAs (DEmRNAs) and lncRN ...[more]

PMID: 30538480

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Project description:INTRODUCTION: In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD. METHODS: An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation. RESULTS: Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes. CONCLUSIONS: This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.

Project description:A hypertrophic scar is the result of abnormal repair of the body after trauma. Histopathologically, it is mostly the result of the excessive proliferation of fibroblasts and the accumulation of extracellular matrix. Accumulating evidence has demonstrated that long non?coding RNAs (lncRNAs) have a critical role in the regulation of gene expression and in the pathogenesis of diseases. However, the roles of lncRNAs in hypertrophic scars have remained elusive. The present study investigated the profiles of differentially expressed lncRNAs between fibroblasts derived from a hypertrophic scar and normal skin, and explored the possible mechanisms underlying the development of hypertrophic scars. Microarray data indicated that 6,104 lncRNAs and 2,952 mRNAs were differentially expressed. A set of differentially expressed transcripts as confirmed by reverse transcription?quantitative polymerase chain reaction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to determine the principal functions of the significantly deregulated genes. Furthermore, associated expression networks, including subgroup analysis, competing endogenous RNAs (ceRNAs) and coding?noncoding co?expression networks were constructed using bioinformatics methods. The homology between differentially expressed lncRNAs and mRNAs was assessed and two exon lncRNA were selected to explore their regulatory mechanisms. The ceRNA network inferred that NR_125715 acted as a competing endogenous RNA, bound to microRNA (miR)?141?3p, miR?200a?3p and miR?29 to regulate the expression of the miRs' targets, including transforming growth factor ?2 (TGFB2). Similarly, NR_046402 acted as a competing endogenous RNA, which bound to miR?133a?3p.1 and miR?4469 to then regulate the expression of the miRs' targets, including DNA polymerase ?1, catalytic subunit (POLD1). In addition, co?expression analysis indicated that the expression of lncRNAs NR_125715 and NR_046402 was correlated with that of TGFB2 and POLD1 mRNA. The identification of these differentially expressed lncRNAs in the hypertrophic scar?derived fibroblasts in the present study, may provide novel insight into the functional interactions of lncRNA, miRNA and mRNA, and lead to novel theories for the pathogenesis and treatment of hypertrophic scars.

Project description:BACKGROUND:Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells (NPCs), especially their biological behavior under the influence of exogenous stem cells, specifically the gene expression and regulation pattern. In the present study, we aimed to determine messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), which are differentially expressed during the co-culturing process with adipose-derived mesenchymal stem cells (ASCs) and to explore the involved signaling pathways and the regulatory networks. METHODS:We compared degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA-mRNA microarray analysis. Based on these data, we investigated the significantly regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were demonstrated to be involved in IDD were chosen; we investigated their theoretic regulatory importance associated with our microarray data. RESULTS:We found 632 lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716 probes. We then confirmed the microarray data by real-time PCR. Furthermore, we demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176 significantly enriched pathways, such as the mitogen-activated protein kinase (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network was constructed for the significantly changed mRNAs and lncRNAs. Also, the competing endogenous RNA (ceRNA) network was built. CONCLUSION:Our results present the first comprehensive identification of differentially expressed lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and outline the gene expression regulation pattern. These may provide valuable information for better understanding of stem cell therapy and potential candidate biomarkers for IDD treatment.

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Aberrantly expressed long noncoding RNAs and genes in Parkinson's disease.

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Aberrantly expressed long noncoding RNAs and genes in Parkinson's disease.

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