Differentially-expressed mRNAs, microRNAs and long noncoding RNAs in intervertebral disc degeneration identified by RNA-sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE167199 | GEO | 2022/02/08
REPOSITORIES: GEO
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Project description:In addition to the well-known short noncoding RNAs as 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, there is relative paucity of information regarding the role of lncRNAs in intervertebral disc degeneration (IDD) hitherto. We have addressed the expression profiles of miRNAs in IDD previously. To determine whether lncRNAs is differentially expressed in IDD, we employed a lncRNA-mRNA microarray analysis of human nucleus pulposus (five degenerative as IDD and five normal specimens as control). With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, microarray data profiling indicated that 18995 lncRNAs and 14635 mRNAs were detected in all samples with 2309 lncRNAs and 3017 mRNAs differentially expressed in degenerated samples. Amongst them, 164 lncRNAs (97 up and 67 down) and 265 mRNAs were highly differentially expressed with an absolute fold change greater than ten. The upregulated mRNAs included the extracellular matrix components as COL1A2, LUM, FN1ACAN, DCN and ITFG2. 1100 lncRNAs and 1379 mRNAs were altered in the same direction in at least 4 of the 5 degenerative samples with fold change greater than 2 respectively. Three lncRNAs were chosen for the real-time quantitative PCR (qRT-PCR) analysis. qRT-PCR results showed a high consistency with the microarray data. In this study, to explore the potential involvement of lncRNAs in IDD, we conducted lncRNA and mRNA profiling in 5 human control nucleus pulposus tissue and 5 degenerative nucleus pulposus tissue by microarray.Biological replicates: 5 control, 5 degenerated, independently harvested.
2014-11-17 | E-GEOD-56081 | biostudies-arrayexpress
Project description:Intervertebral disc degeneration (IDD) leads to low back pain and disability globally. The pathophysiology of IDD is not entirely understood. There is increasing evidence that long noncoding RNAs (lncRNAs) play a key regulatory role in a wide range of biological processes. The purpose of this study was to comprehensively lncRNA and mRNA expression profiles of human intervertebral disc (IVD) tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. The overview of lncRNA and mRNA expression profiles in the current study revealed that differentially expressed lncRNAs and mRNAs were identified that have been reported to be relevant to IDD. Importantly, differentially expressed lncRNAs and mRNAs that regulate the major signaling pathways, such as NF-κB, MAPK, and Wnt signaling, that are well known to be responsible for the pathogenesis of IDD.
2023-02-09 | GSE186542 | GEO
Project description:In addition to the well-known short noncoding RNAs as 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, there is relative paucity of information regarding the role of lncRNAs in intervertebral disc degeneration (IDD) hitherto. We have addressed the expression profiles of miRNAs in IDD previously. To determine whether lncRNAs is differentially expressed in IDD, we employed a lncRNA-mRNA microarray analysis of human nucleus pulposus (five degenerative as IDD and five normal specimens as control). With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, microarray data profiling indicated that 18995 lncRNAs and 14635 mRNAs were detected in all samples with 2309 lncRNAs and 3017 mRNAs differentially expressed in degenerated samples. Amongst them, 164 lncRNAs (97 up and 67 down) and 265 mRNAs were highly differentially expressed with an absolute fold change greater than ten. The upregulated mRNAs included the extracellular matrix components as COL1A2, LUM, FN1ACAN, DCN and ITFG2. 1100 lncRNAs and 1379 mRNAs were altered in the same direction in at least 4 of the 5 degenerative samples with fold change greater than 2 respectively. Three lncRNAs were chosen for the real-time quantitative PCR (qRT-PCR) analysis. qRT-PCR results showed a high consistency with the microarray data.
2014-11-17 | GSE56081 | GEO
Project description:Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the most common cause of acute respiratory deterioration and death in IPF patients, with an elusive etiology and pathogenesis. Roles of noncoding RNAs in AE-IPF have been proposed, however, it was rare to find studies have systematically investigated the crosstalk among various transcripts until now. The construction of RNA functional networks such as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interaction networks could therefore facilitate our understanding of RNA interactions in AE-IPF. The study aimed to identify the expression differences of RNA transcripts in RNA sequencing from AE-IPF patients and stable IPF (S-IPF), and further to construct the potential RNA networks. Methods: Five AE-IPF patients and five S-IPF were recruited in this study to perform RNA sequencing and miRNA sequencing. The differentially expression profiles of lncRNAs, circRNAs, miRNAs and mRNAs between AE-IPF and S-IPF patients were identified for further analyses. Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of were performed. The competing endogenous RNAs (ceRNAs) network of lncRNA/circRNA-miRNA-mRNA was constructed, and the core regulatory molecules in the ceRNA network were analyzed. Results: A total of 69 lncRNAs, 150 circRNAs, 27 miRNAs and 56 mRNAs were differentially expressed between AE-IPF and S-IPF. GO and KEGG analysis show that differentially expression mRNAs are significantly associated with tight junction and Hepatitis C, etc. In the ceRNA network, all nodes are directly or indirectly involved in the progression of AE-IPF. 1 lncRNAs, 6 circRNAs, 1 miRNAs, and 5 mRNAs constituted a hsa-miR-150-5p core sub-network. Based on the analysis of ceRNA sub-network, NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 were considered to be the key ceRNA axis. Conclusions: In conclusion, this study reveals NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 may be the key ceRNA axis in the regulation of AE-IPF, providing clues for future studies on their roles for AE-IPF. Our findings will help to explore the pathological mechanism of AE-IPF from a transcriptomic perspective and provide enlightenment for the biomarker and therapeutic targets of AE-IPF.
2023-12-31 | GSE222065 | GEO
Project description:Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the most common cause of acute respiratory deterioration and death in IPF patients, with an elusive etiology and pathogenesis. Roles of noncoding RNAs in AE-IPF have been proposed, however, it was rare to find studies have systematically investigated the crosstalk among various transcripts until now. The construction of RNA functional networks such as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interaction networks could therefore facilitate our understanding of RNA interactions in AE-IPF. The study aimed to identify the expression differences of RNA transcripts in RNA sequencing from AE-IPF patients and stable IPF (S-IPF), and further to construct the potential RNA networks. Methods: Five AE-IPF patients and five S-IPF were recruited in this study to perform RNA sequencing and miRNA sequencing. The differentially expression profiles of lncRNAs, circRNAs, miRNAs and mRNAs between AE-IPF and S-IPF patients were identified for further analyses. Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of were performed. The competing endogenous RNAs (ceRNAs) network of lncRNA/circRNA-miRNA-mRNA was constructed, and the core regulatory molecules in the ceRNA network were analyzed. Results: A total of 69 lncRNAs, 150 circRNAs, 27 miRNAs and 56 mRNAs were differentially expressed between AE-IPF and S-IPF. GO and KEGG analysis show that differentially expression mRNAs are significantly associated with tight junction and Hepatitis C, etc. In the ceRNA network, all nodes are directly or indirectly involved in the progression of AE-IPF. 1 lncRNAs, 6 circRNAs, 1 miRNAs, and 5 mRNAs constituted a hsa-miR-150-5p core sub-network. Based on the analysis of ceRNA sub-network, NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 were considered to be the key ceRNA axis. Conclusions: In conclusion, this study reveals NR_120628/hsa-miR-150-5p/E2F3 and has-circ-0053515/hsa-miR-150-5p/E2F3 may be the key ceRNA axis in the regulation of AE-IPF, providing clues for future studies on their roles for AE-IPF. Our findings will help to explore the pathological mechanism of AE-IPF from a transcriptomic perspective and provide enlightenment for the biomarker and therapeutic targets of AE-IPF.
2023-12-31 | GSE221937 | GEO
Project description:In this research, we investigated the abnormal expression of lncRNA and established lncRNA-associated ceRNA regulatory networks composed of potential therapeutic targets in AD based on RNA sequencing (RNA-seq) analysis and experimental verification. RNA-seq was performed in the cerebral cortex and hippocampus of 5×FAD mice of AD to systematically investigate altered lncRNA-associated ceRNA regulatory network, along with qualitative analyses for key differentially expressed lncRNAs, miRNAs, and mRNAs involved. The results showed that 7 lncRNAs were significantly altered in the cortex and hippocampus of 5×FAD mice compared with WT mice. The potential functions of differentially expressed genes were highly correlated with learning and memory activities and the pathogenesis of AD. Furthermore, lncRNA Xist and highly correlated miRNAs and mRNAs were identified as key mediators of pathophysiological processes in AD. Our findings illustrated the AD-derived lncRNA-mediated ceRNA network, accompanied by aberrant expression involved in the pathological gene networks, which may contribute to understanding the pathological mechanism of AD and provide potential therapeutic targets for drug development.
2022-12-07 | GSE206562 | GEO
Project description:Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. Here we investigate the localization mechanisms of Xist during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X-chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X-chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X-chromosome. Xist initially accumulates on the periphery of actively transcribed regions and requires its silencing domain to spread across active regions. This suggests a model where Xist coats the entire X-chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations. We examined the genomic localization of the Xist lncRNA using RNA Antisense Purification (RAP) in multiple cell contexts: 1) differentiated female cells (MLFs); 2) a time-course of Xist localization in male embryonic stem (ES) cells where the endogenous Xist promoter is replaced by a tet-inducible one (pSM33); 3) a time-course of Xist localization in differentiating female ES cells (F1 2-1); and 4) wild-type (delXF6) and A-repeat deletion (delSXC9) Xist transgenes incorporated into the Hprt locus under the control of a tet-inducible promoter.
2013-05-30 | E-GEOD-46918 | biostudies-arrayexpress
Project description:The metabolic syndrome (MetS), a collective cluster of disease risk factors that includes dyslipidemia, obesity, inflammation, hypertension, and insulin resistance, affects numerous people worldwide. Accumulating studies have shown that long-noncoding RNAs (lncRNA) serve as competing endogenous RNA (ceRNA) to play essential roles in regulating gene expression in various diseases. To explore the role of lncRNAs as ceRNAs in MetS, we examined a MetS-associated network in circulating extracellular vesicles (EVs) collected from systemic blood of MetS and control patients (n=5 each). MetS patients showed elevated body-weight, glucose, blood pressure, insulin, liver injury and inflammatory markers levels. In total, 191 differentially-expressed (DE) lncRNAs, 1389 mRNAs, and 138 miRNAs were selected for further analysis. Biological processes and pathway functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. LncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.8 based on the DE-RNAs, and included 13 lncRNAs, 8 miRNAs, and 64 mRNAs. We found that the lncRNA-associated ceRNA network members potentially serve as regulators of central cellular processes and complications of MetS, including cancer. These findings suggest that MetS alters the interactions among the ceRNA network components in circulating EV-specific ceRNA network, and implicate the cargo of circulating EVs in ramifications of MetS.
2021-02-10 | GSE166474 | GEO
Project description:Abstract: Backgroud: This study was to explore long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles and construct functional networks to analyze their biological functions when botulinum toxin type A (BTXA) inhibited salivary secretion. Methods: BTXA and saline were injected into the submandibular gland of rats as the BTXA group and control group, respectively. Morphological and secretory function tests validated the animal models. Microarray analysis was applied to identify the expression variation of lncRNA and mRNA and were confirmed by qRT-PCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explicit the biological functions. The construction of functional networks including lncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network was to reveal the interaction between coding and noncoding genes. Results: A total of 254 lncRNAs and 631 mRNAs were differentially expressed (DE) between the control group and the BTXA group. Ten lncRNAs and eleven mRNAs were confirmed by qRT-PCR and the results were consistent with the microarray analysis. The bioinformatic analysis found that most of mRNAs were closely related to transmembrane transporter activity. LncRNA-mRNA co-expression network and ceRNA network were constructed and identified several critical mRNA-lncRNA axes and key microRNAs related to salivary secretion, respectively. Conclusions: Our study identified DE lncRNAs and mRNAs through microarray analysis and explored the biological functions and interaction between coding and noncoding genes through bioinformatics analysis. These findings may provide new directions for the mechanism of BTXA to inhibit salivary secretion.
2020-06-30 | GSE144985 | GEO
Project description:This study constructed a ceRNA network consisting of lncRNA–miRNA–mRNA based on lncRNA-mRNA and miRNA-mRNA interactions. Our objective was to investigate functional modules and hub differentially expressed genes, miRNAs and lncRNAs on different traits.
2022-05-18 | GSE159902 | GEO