Dataset Information

Lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes.

ABSTRACT: Osteoarthritis (OA) is the most common motor system disease in aging people, characterized by matrix degradation, chondrocyte death, and osteophyte formation. OA etiology is unclear, but long noncoding RNAs (lncRNAs) that participate in numerous pathological and physiological processes may be key regulators in the onset and development of OA. Because profiling of lncRNAs and their biological function in OA is not understood, we measured lncRNA and mRNA expression profiles using high-throughput microarray to study human knee OA. We identified 2,042 lncRNAs and 2,011 mRNAs that were significantly differentially expressed in OA compared to non-OA tissue (>2.0- or < - 2.0-fold change; p < 0.5), including 1,137 lncRNAs that were upregulated and 905 lncRNAs that were downregulated. Also, 1,386 mRNA were upregulated and 625 mRNAs were downregulated. QPCR was used to validate chip results. Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes was used to study the biological function enrichment of differentially expressed mRNA. Additionally, coding-non-coding gene co-expression (CNC) network construction was performed to explore the relevance of dysregulated lncRNAs and mRNAs. Finally, the gain/loss of function experiments of lnc-SAMD14-4 was implemented in IL-1?-treated human chondrocytes. In general, this study provides a preliminary database for further exploring lncRNA-related mechnisms in OA.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6727836 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes.

Zhang Haibin H Chen Cheng C Cui Yinghong Y Li Yuqing Y Wang Zhaojun Z Mao Xinzhan X Dou Pengcheng P Li Yihan Y Ma Chi C

PeerJ 20190902

Osteoarthritis (OA) is the most common motor system disease in aging people, characterized by matrix degradation, chondrocyte death, and osteophyte formation. OA etiology is unclear, but long noncoding RNAs (lncRNAs) that participate in numerous pathological and physiological processes may be key regulators in the onset and development of OA. Because profiling of lncRNAs and their biological function in OA is not understood, we measured lncRNA and mRNA expression profiles using high-throughput m ...[more]

PMID: 31534838

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Project description:Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

Dataset Information

Lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes.

Publications

lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes.

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