Dataset Information

The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis.

ABSTRACT: Mechanical stress plays a key role in the development of cartilage degradation in osteoarthritis (OA). Nevertheless, the role of long noncoding RNAs in mechanical stress-induced regulation of chondrocytes remains unclear. The aim of this study was to explore the function of mechanical stress-related long noncoding RNAs in cartilage. Tissue samples were collected from 50 patients and chondrocytes were exposed to cyclic tensile strain (CTS). A total of 107 lncRNAs were differentially expressed in damaged cartilage versus intact cartilage. Of these lncRNAs, 51 were upregulated and 56 were downregulated in the damaged tissue. The TMSB4 pseudogene, lncRNA-MSR, was upregulated in the damaged cartilage and was activated in chondrocytes in response to mechanical stress. Furthermore, lncRNA-MSR regulated the expression of TMSB4 by competing with miRNA-152 in chondrocytes. Our results demonstrated that upregulation of lncRNA-MSR initiates pathological changes that lead to cartilage degradation, and the inhibition of lncRNA-MSR could represent a potential therapeutic target for OA.

SUBMITTER: Liu Q

PROVIDER: S-EPMC5112043 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis.

Liu Qiang Q Hu Xiaoqing X Zhang Xin X Dai Linghui L Duan Xiaoning X Zhou Chunyan C Ao Yingfang Y

Molecular therapy : the journal of the American Society of Gene Therapy 20160729 10

Mechanical stress plays a key role in the development of cartilage degradation in osteoarthritis (OA). Nevertheless, the role of long noncoding RNAs in mechanical stress-induced regulation of chondrocytes remains unclear. The aim of this study was to explore the function of mechanical stress-related long noncoding RNAs in cartilage. Tissue samples were collected from 50 patients and chondrocytes were exposed to cyclic tensile strain (CTS). A total of 107 lncRNAs were differentially expressed in ...[more]

PMID: 27469625

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Project description:BackgroundOsteoarthritis (OA) is one of the most common diseases in elderly people; however, the correlation between molecular alterations and the occurrence and progression of OA are still not well understood. We conducted this study to investigate the molecular changes in OA via the competing endogenous ribonucleic acid (ceRNA) network.MethodsWe downloaded the messenger RNA (mRNA) data set, GSE48556, the microRNA (miRNA) data set, GSE105027, and the long non-coding (lncRNA) data set, GSE126963 from the Gene Expression Omnibus (GEO) database, and examined the differentially expressed genes (DEGs) in these data sets. Further, we constructed a ceRNA network of the differentially expressed miRNAs, mRNAs, and lncRNAs. To determine the biological functions of the ceRNA network, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Finally, we conducted an immune cell infiltration analysisusing single-sample gene set enrichment analysis to examine the abundance of immune cells in healthy and OA patients, and compared the infiltration of 28 immune cells between the healthy and OA samples. We also analyzed the relationship between the abundance of immune cells and mRNA expression levels in the ceRNA network.ResultsUltimately hsa-mir-425-3p, dual specificity phosphatase 1, and 24 lncRNAs were identified in the ceRNA network. The functional enrichment analyses showed that these lncRNAs, miRNAs, and mRNAs are involved in various significant biological process, such as the regulation of leukocyte migration, Mitogen-Activated Protein (MAP) kinase tyrosine/serine/threonine phosphatase activity, the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and osteoclast differentiation, and can also have a strong effect on immune cell infiltration.ConclusionsThe dual-specificity phosphatase 1-specific ceRNA network can be used as a diagnostic tool to assess the progression of OA patients.

Dataset Information

The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis.

Publications

The TMSB4 Pseudogene LncRNA Functions as a Competing Endogenous RNA to Promote Cartilage Degradation in Human Osteoarthritis.

Similar Datasets

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