Dataset Information

Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data.

ABSTRACT: Our study intended to identify potential long non-coding RNAs (lncRNAs) and genes, and to elucidate the underlying mechanisms of intervertebral disc degeneration (IDD).The microarray of GSE56081 was downloaded from the Gene Expression Omnibus database, including 5 human control nucleus pulposus tissues and 5 degenerative nucleus pulposus tissues, which was on the basis of GPL15314 platform. Identification of differentially expressed lncRNAs and mRNAs were performed between the 2 groups. Then, gene ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways for the differentially expressed mRNAs. Simultaneously, lncRNA-mRNA weighted coexpression network was constructed using the WGCNA package, followed by GO and KEGG pathway enrichment analyses for the genes in the modules. Finally, the protein-protein interaction (PPI) network was visualized.A total of 135 significantly up- and 170 down-regulated lncRNAs and 2133 significantly up- and 1098 down-regulated mRNAs were identified. Additionally, UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1), with the highest connectivity degree in PPI network, was remarkably enriched in the pathway of metabolism of proteins. Eight lncRNAs - LINC00917, CTD-2246P4.1, CTC-523E23.5, RP4-639J15.1, RP11-363G2.4, AC005082.12, MIR132, and RP11-38F22.1 - were observed in the modules of lncRNA-mRNA weighted coexpression network. Moreover, SPHK1 in the green-yellow module was significantly enriched in positive regulation of cell migration.LncRNAs LINC00917, CTD-2246P4.1, CTC-523E23.5, RP4-639J15.1, RP11-363G2.4, AC005082.12, MIR132, and RP11-38F22.1 were differentially expressed and might play important roles in the development of IDD. Key genes, such as UBA52 and SPHK1, may be pivotal biomarkers for IDD.

SUBMITTER: Chen Y

PROVIDER: S-EPMC4646231 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data.

Chen Yu Y Ni Haijian H Zhao Yingchuan Y Chen Kai K Li Ming M Li Cheng C Zhu Xiaodong X Fu Qiang Q

Medical science monitor : international medical journal of experimental and clinical research 20151110

<h4>Background</h4>Our study intended to identify potential long non-coding RNAs (lncRNAs) and genes, and to elucidate the underlying mechanisms of intervertebral disc degeneration (IDD).<h4>Material and methods</h4>The microarray of GSE56081 was downloaded from the Gene Expression Omnibus database, including 5 human control nucleus pulposus tissues and 5 degenerative nucleus pulposus tissues, which was on the basis of GPL15314 platform. Identification of differentially expressed lncRNAs and mRN ...[more]

PMID: 26556537

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Project description:Background: Intervertebral disc degeneration (IDD) entails complex pathological changes and causes lower back pain (LBP). However, there is still a lack of understanding of the mechanisms involved in IDD, particularly regarding the roles of autophagy and ferroptosis. The current study used microarray data to investigate the pathogenesis of IDD and potential biomarkers related to autophagy and ferroptosis in IDD. Methods: Differentially expressed genes (DEGs) were identified by analyzing the mRNA and miRNA expression profiles of IDD patients from the Gene Expression Omnibus (GEO). The protein-protein interaction network, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were utilized. The Human Autophagy Database (HADb) and Ferroptosis Database were used in conjunction with hub genes to identify autophagy- and ferroptosis-related genes. The Transcription Factor -hub gene-miRNA network was constructed. Lastly, the expression of DEGs in normal and degenerated nucleus pulposus cells (NPCs) was investigated via the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: A total of 362 DEGs associated with IDD were identified. GO and KEGG analyses indicated that oxidative stress, extracellular matrix, PI3K-AKT signaling pathway, and ferroptosis were key factors in IDD occurrence. GSEA indicated that IDD was associated with changes in autophagy, iron ion homeostasis, extracellular matrix, and oxidative stress. Eighty-nine hub genes were obtained, including five that were autophagy-related and three that were ferroptosis-related. Of these, TP53 and SESN2 were the intersections of autophagy- and ferroptosis-related genes. In qRT-PCR analysis, CANX, SLC38A1, and TP53 were downregulated in degenerative NPCs, whereas GNAI3, SESN2, and VAMP3 were upregulated. Conclusion: The current study revealed aspects of autophagy- and ferroptosis-related genes involved in IDD pathogenesis, warranting further investigation.

Project description:BackgroundLong non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas.Methodology/principal findingsIn this study, we described the lncRNA profiles in six preeclampsia placentas (T) and five normal pregnancy placentas (N) using microarray. With abundant and varied probes accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were expressed at a specific level were detected. From the data, we found 738 lncRNAs that were differentially expressed (≥ 1.5-fold-change) among preeclampsia placentas compared with controls. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. According to the CNC network and GO analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40 controls. These results revealed that three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls.Conclusions/significanceOur study is the first study to determine the genome-wide lncRNAs expression patterns in preeclampsia placenta using microarray. These results revealed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which indicated that lncRNAs differentially expressed in preeclampsia placenta might play a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, and CEACAMP8 might contribute to the mechanism underlying preeclampsia. Taken together, this study may provide potential targets for the future treatment of preeclampsia and novel insights into preeclampsia biology.

Project description:Background: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. We want to study the lncRNAs profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent demonstrating that the placenta is sufficient to cause the condition. So we analyze the lncRNAs profiles in preeclampsia placentas. In this study, we described the lncRNAs profiles in 6 preeclampsia placentas (T) and 5 matched normal pregnancy placentas (N) tissues by microarray. Methodology/Principal Findings: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 28,443. From the data we found there were 738 lncRNAs that differentially expressed (M-bM-^IM-%1.5 fold-change) among preeclampsia placentas compared with matched controls. Up to 18,063 coding transcripts could be detected in placenta samples through 30,215 coding transcripts probes. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs. According to the GO-Pathway analysis of differential expressed lncRNAs/mRNAs, we choose three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, CEACAMP8 were evaluated by qPCR in 40 of preeclampsia placentas and 40 of controls. The results showed three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. Conclusions/Significance: Our study is the first one to determine genome-wide lncRNAs expression patterns in preeclampsia placenta by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which revealed that lncRNAs differentially expressed in preeclampsia placenta may exert a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, CEACAMP8 might be associated with preeclampsia. Taken together, this study may provide potential targets for future treatment of preeclampsia and novel insights into preeclampsia biology. LncRNAs/mRNAs profiles in 6 preeclampsia placentas and 5 matched normal pregnancy placentas tissues by microarray using Arraystar v2.0.

Project description:Long non-coding RNAs (lncRNAs) have been acknowledged to serve a significant role in cancer biology and abnormal expression in tumors is frequently observed. However, their mechanisms in cervical cancer remain unclear. With a genome-wide analysis of lncRNA expression in cervical cancer tissues, the present study aimed to identify lncRNA targets for the further study of cervical cancer. To elucidate the specific role of lncRNAs in the pathogenesis of this type of cancer, 6 cervical cancer samples paired with normal cervical tissues were obtained. Expression profiles of lncRNAs and mRNAs were constructed through microarray analysis and confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methods. Gene Ontology and pathway enrichment analyses were performed with computational methods. On the basis of correlations between the differential expression levels of lncRNAs and mRNAs, a coding-non-coding gene co-expression network (CNC network) was established. The differential expression of 5,844 lncRNAs and 4,436 mRNAs were discovered in cervical cancer samples compared with normal cervical tissues. Among the differentially expressed lncRNAs, 14 were chosen at random and validated by RT-qPCR; the majority of the results measured were consistent with the microarray results. Furthermore, the lncRNA ENST00000551152 was found to be upregulated and TCO. NS_00001368 lncRNA was downregulated in cervical cancer cell lines. The CNC network included 592 network nodes and 934 associations between 12 lncRNAs and 580 protein-coding genes, indicating that one lncRNA could act on a maximum of 141 coding genes, and that one coding gene may corresponded with a maximum of 5 lncRNAs. Overall, the present study has provided a complete expression profile of lncRNAs and mRNAs in cervical cancer, which may now be used to establish a solid foundation for cervical cancer research. These results may provide significant information for improving the understanding of the pathogenesis of cervical cancer and indicate potential therapeutic targets.

Dataset Information

Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data.

Publications

Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data.

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