Dataset Information

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

ABSTRACT: BACKGROUND:It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD. METHODS:A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were used to investigate gene expression levels. Cell transfections were carried out to analyze gene interactions. The diagnostic value of lncRNA MAGI2-AS3 for IDD was assessed by ROC curve analysis. RESULTS:The expression levels of plasma lncRNA MAGI2-AS3 were lower in IDD patients compared to that in the control group. Down-regulation of lncRNA MAGI2-AS3 effectively distinguished IDD patients from the control group. The expression levels of plasma lncRNA MAGI2-AS3 were significantly increased after the treatments. Over-expression of lncRNA MAGI2-AS3 inhibited the expression of FasL, while the silencing of lncRNA MAGI2-AS3 promoted the expression of FasL in nucleus pulposus (NP) cells. CONCLUSIONS:Therefore, lncRNA MAGI2-AS3 is down-regulated in IDD and participates in the regulation of FasL expression in nucleus pulposus (NP) cells.

SUBMITTER: Cui S

PROVIDER: S-EPMC7059357 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

Cui Shuting S Liu Zizhen Z Tang Bin B Wang Zhizhen Z Li Baojian B

BMC musculoskeletal disorders 20200306 1

<h4>Background</h4>It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD.<h4>Methods</h4>A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were u ...[more]

PMID: 32143617

Similar Datasets

Project description:Intervertebral disc (IVD) degeneration is a complicated physiological change involving cellular senescence, inflammation and the degradation of the extracellular matrix. Long non?coding RNAs (lncRNAs) have been identified as new players in IVD degeneration. The present study aimed to identify lncRNAs implicated in IVD degeneration via the regulation of cellular senescence. In the present study, nucleus pulposus (NP) cells isolated from moderately degenerated IVD tissues exhibited a senescent phenotype with increased senescence rates, detected by senescence?associated ??galactosidase (SA???gal) staining, and reduced growth and migratory abilities. Microarray and target prediction analyses identified 353 differentially expressed lncRNAs, and 251 cis? and 2,170 trans?acting targets in degenerated NP cells. Bioinformatic analyses revealed that these predicted targets were enriched in the regulation of response to DNA damage stimulus, positive regulation of cell cycle processes and interferon?? production. In addition, a network of the top 10 upregulated and top 10 downregulated lncRNA targets was constructed, and two trans?acting targets, C?C motif chemokine ligand 5 (CCL5) and polyribonucleotide nucleotidyltransferase 1 (PNPT1) involved in aging or senescence, and their corresponding lncRNAs, lnc?ST8SIA5?1:2 and lnc?HRK?2:1, were identified. Reverse transcription?quantitative PCR validation demonstrated that the two targets and two candidate lncRNAs were significantly upregulated in degenerated NP cells. Overexpression of lnc?HRK?2:1, with validated higher expression levels, in normal NP cells induced a senescent phenotype, with enhanced rates of senescence detected by SA???gal staining in cells, decreased growth and migratory abilities and improved expression levels of CCL5 and PNPT1. Collectively, these results suggested that upregulation of lnc?HRK?2:1 prompted NP cell senescence in IVD degeneration, which may be associated with increased expression levels of CCL5 and PNPT1.

Project description:STUDY DESIGN:Profiling proteins expressed in the nucleus pulposus of fetal intervertebral disc (IVD). PURPOSE:To evaluate the molecular complexity of fetal IVDs not exposed to mechanical, traumatic, inflammatory, or infective insults to generate improved knowledge on disc homeostasis. OVERVIEW OF LITERATURE:Low back pain is the most common musculoskeletal disorder, causing a significant reduction in the quality of life, and degenerative disc disorders mainly contribute to the increasing socioeconomic burden. Despite extensive research, the causative pathomechanisms behind degenerative disc disorders are poorly understood. Precise molecular studies on the intricate biological processes involved in maintaining normal disc homeostasis are needed. METHODS:IVDs of nine fetal specimens obtained from medical abortions were used to dissect out the annulus fibrosus and nucleus pulposus under sterile operating conditions. Dissected tissues were transferred to sterile Cryovials and snap frozen in liquid nitrogen before transporting to the research laboratory for protein extraction and further liquid chromatography tandem mass spectrometry (LC-MS/ MS) analysis. Collected data were further analyzed using Gene Functional Classification Tool in DAVID and STRING databases. RESULTS:A total of 1,316 proteins were identified through LC-MS/MS analysis of nine fetal IVD tissues. Approximately 247 proteins present in at least four fetal discs were subjected to further bioinformatic analysis. The following 10 clusters of proteins were identified: collagens, ribosomal proteins, small leucine-rich proteins, matrilin and thrombospondin, annexins, protein disulfide isomerase family proteins and peroxiredoxins, tubulins, histones, hemoglobin, and prolyl 4-hydroxylase family proteins. CONCLUSIONS:This study provides fundamental information on the proteome networks involved in the growth and development of healthy fetal discs in humans. Systematic cataloging of proteins involved in various structural and regulatory processes has been performed. Proteins expressed most abundantly (collagen type XIV alpha 1 chain, biglycan, matrilin 1, and thrombospondin 1) in their respective clusters also elucidate the possibility of utilizing these proteins for potential regenerative therapies.

Project description:BACKGROUND:Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Although the mechanism of degeneration remains unclear, aging has been recognized as a key risk factor for IVDD. Most studies seeking to identify IVDD-associated molecular alterations in the context of human age-related IVDD have focused only on a limited number of proteins. Differential proteomic analysis is an ideal method for comprehensively screening altered protein profiles and identifying the potential pathways related to pathological processes such as disc degeneration. METHODS:In this study, tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of human fetal and geriatric lumbar disc nucleus pulposus (NP) tissue. Parallel reaction monitoring (PRM) and Western blotting (WB) techniques were used to identify target proteins. Bioinformatic analyses, including Gene Ontology (GO) annotation, domain annotation, pathway annotation, subcellular localization and functional enrichment analyses, were used to interpret the potential significance of the protein alterations in the mechanism of IVDD. Student's t-tests and two-tailed Fisher's exact tests were used for statistical analysis. RESULTS:Six hundred forty five proteins were significantly upregulated and 748 proteins were downregulated in the geriatric group compared with the fetal group. Twelve proteins were verified to have significant differences in abundance between geriatric and fetal NP tissue; most of these have not been previously identified as being associated with human IVDD. The potential significance of the differentially expressed proteins in age-related IVDD was analyzed from multiple perspectives, especially with regard to the association of the immunoinflammatory response with IVDD. CONCLUSIONS:Differential proteomic analysis was used as a comprehensive strategy for elucidating the protein alterations associated with age-related IVDD. The findings of this study will aid in the screening of new biomarkers and molecular targets for the diagnosis and therapy of IVDD. The results may also significantly enhance our understanding of the pathophysiological process and mechanism of age-related IVDD.

Dataset Information

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

Publications

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure