Dataset Information

Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration.

ABSTRACT: The present study aimed to identify novel intervertebral disc degeneration (IDD)?associated long noncoding (lnc)RNAs and genes. The lncRNA and mRNA microarray dataset GSE56081 was downloaded from the Gene Expression Omnibus database and included 5 samples from patients with degenerative lumbar nucleus pulposus and 5 normal controls. Differentially expressed lncRNAs or differentially expressed genes (DEGs) were identified and co?expression network analysis was performed followed by functional analysis for genes in the network. Additionally, a microRNA (miRNA)?lncRNA?mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on DEGs and lncRNAs in the co?expression network. Furthermore, a literature search was performed to identify specific miRNAs that had been previously associated with IDD and a specific miRNA?associated ceRNA network was extracted from the co?expression network. A total of 967 genes and 137 lncRNAs were differentially expressed between IDD samples and controls. A co?expression network was constructed and contained 39 differentially expressed lncRNAs and 209 DEGs, which were primarily involved in 'skeletal system development', 'response to mechanical stimulus' and 'bone development'. Furthermore, a ceRNA network was established, including 79 miRNAs, 9 downregulated lncRNAs and 148 DEGs. The identified miRNAs included a previously reported disease?associated miRNA, hsa?miR?140. The present study demonstrated that hsa?miR?140 was regulated by three lncRNAs in the hsa?miR?140?associated ceRNA network, including KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), OIP5 antisense RNA 1 (OIP5?AS1) and UGDH antisense RNA 1 (UGDH?AS1). KCNQ1OT1 was co?expressed with neurochondrin (NCDN) and lon peptidase 2, peroxisomal. In addition, the lncRNAs OIP5?AS1 and UGDH?AS1 targeted several overlapping co?expressed genes, including forkhead box F1 (FOXF1) and polycystin 1, transient receptor potential channel interacting (PKD1). Therefore, KCNQ1OT1 may regulate the expression of NCDN, and OIP5?AS1 and UGDH?AS1 may affect the expression of FOXF1 and PKD1 in IDD. Further experiments are required to validate the results of the present study, which may provide valuable insights into the identification of novel biomarkers associated with IDD.

SUBMITTER: Qu Z

PROVIDER: S-EPMC6072222 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration.

Qu Zhigang Z Quan Zhe Z Zhang Qi Q Wang Zhenyu Z Song Qingxu Q Zhuang Xinming X Fu Changfeng C Xu Feng F Liu Yadong Y Wang Yuanyi Y Wang Zheng Z Liu Yi Y

Molecular medicine reports 20180605 2

The present study aimed to identify novel intervertebral disc degeneration (IDD)‑associated long noncoding (lnc)RNAs and genes. The lncRNA and mRNA microarray dataset GSE56081 was downloaded from the Gene Expression Omnibus database and included 5 samples from patients with degenerative lumbar nucleus pulposus and 5 normal controls. Differentially expressed lncRNAs or differentially expressed genes (DEGs) were identified and co‑expression network analysis was performed followed by functional ana ...[more]

PMID: 29901136

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Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)‑mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA‑miRNA‑mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), mitogen‑activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit α (HIF1A) and transforming growth factor β1 (TGFB1) were hub genes and enriched in modules. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348‑hsa‑miR‑185‑5p‑TGFB1/FOS, MALAT1‑hsa‑miR‑155‑5p‑HIF1A, hsa_circRNA_102399‑hsa‑miR‑302a‑3p‑HIF1A, MALAT1‑hsa‑miR‑519d‑3p‑MAPK1 and hsa_circRNA_100086‑hsa‑miR‑509‑3p‑MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.

Dataset Information

Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration.

Publications

Comprehensive evaluation of differential lncRNA and gene expression in patients with intervertebral disc degeneration.

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