The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis

Su, Wei; Xie, Wen; Shang, Qingkun; Su, Bing

doi:10.1155/2015/356893

Cited by 117 publications

(98 citation statements)

References 20 publications

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“…Long noncoding RNAs (LncRNAs) are longer than 200 nucleotides (nts) in length with no or limited protein‐coding capacity and were found to play important roles in diverse human diseases and biological processes . Mounting evidence has suggested that many lncRNAs are beregulated in diverse diseases such as tumours, diabetes, coronary heart disease, osteoarthritis and also IDD . For example, Lan and colleagues profiled lncRNA expression in degenerate disc tissues and normal adults' lumbar discs by microarray and found a total of 3081 differentially expressed lncRNAs.…”

Section: Introductionmentioning

confidence: 99%

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

Wang

Peng

Gong

et al. 2018

J Cellular Molecular Medi

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Long noncoding RNAs (LncRNAs) are involved in the pathogenesis of intervertebral disc degeneration (IDD). However, the biological function and expression of RMRP were still unclear. In our study, we showed that RMRP expression was up‐regulated in degenerated NP tissues compared to normal NP samples, and higher RMRP expression was associated with the disc degeneration grade. Further studies indicated that ectopic expression of RMRP enhanced NP cell growth and also enhanced the expression of ki‐67, PCNA and cyclin D1 in the NP cell. Moreover, overexpression of RMRP promoted the expression of Type II collagen and aggrecan and suppressed the expression of MMP13 and ADAMTS4. In addition, we found that the expression of miR‐206 was down‐regulated in degenerated NP tissues compared to normal NP samples, and lower miR‐206 expression was correlated with the disc degeneration grade. Interestingly, we indicated that miR‐206 expression in NP tissues was negatively correlated with the expression of RMRP. Ectopic expression of miR‐206 suppressed NP cell proliferation and suppressed the expression of Type II collagen and aggrecan and enhanced the expression of MMP13 and ADAMTS4. Furthermore, we demonstrated that overexpression of RMRP increased NP cell growth and regulated ECM expression through targeting miR‐206. These results suggested that lncRNA‐RMRP promoted the progression of IDD through targeting miR‐206, providing an attractive new therapeutic approach for the treatment of IDD disease.

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Section: Introductionmentioning

confidence: 99%

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

Wang

Peng

Gong

et al. 2018

J Cellular Molecular Medi

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“…A number of lncRNAs, including ubiquitin-fold modifier conjugating enzyme 1 (5), HOX transcript antisense RNA (8), maternally expressed 3 (non-protein coding) (19), growth arrest specific 5 (non-protein coding) (7) and imprinted maternally expressed transcript (non-protein coding) (20), were reported to be significantly associated with the progression of OA. However, the functional roles of most lncRNAs in OA remain largely elusive.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of key mRNAs and lncRNAs in osteoarthritis

et al. 2018

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Osteoarthritis (OA) is the most common type of arthritis, observed mainly in the population aged >65 years. However, the mechanism underlying the development and progression of OA has remained largely elusive. The present study aimed to identify differentially expressed mRNAs and lncRNAs in OA. By analyzing the GSE48556 and GSE82107 datasets, a total of 202 up- and 434 downregulated mRNAs were identified in OA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that differently expressed genes were mainly involved in regulating antigen processing and presentation, interspecies interaction between organisms, immune response, transcription and signal transduction. In addition, a series of long non-coding (lnc)RNAs were differently expressed in OA. To provide novel data on the molecular mechanisms and functional roles of these lncRNAs in OA, a co-expression analysis was performed, which revealed that the dysregulated lncRNAs were associated with transcription, signal transduction, immune response and cell adhesion. In addition, certain key genes in protein-protein interaction networks were identified. The present study provided useful information for exploring potential candidate biomarkers for the diagnosis and prognosis of OA, as well as novel drug targets.

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“…Besides miRNAs, lncRNAs also participate in the regulation of angiogenesis. MEG3 is thought to inhibit this process by reducing VEGF levels,[14] and GAS5 knockdown increases retinal neovascularization and capillary leakage. [15] In contrast, the lncRNA MALAT1 can enhance VEGF expression and promote pathological angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-210 Plays a Critical Role in the Angiogenic Effect of Isoprenaline on Human Umbilical Vein Endothelial Cells via Regulation of Noncoding RNAs

Yan

Wang

Zhao

et al. 2016

Chinese Medical Journal

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Background:β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells. Isoprenaline (ISO, a β-adrenergic agonist) has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor (VEGF) expression; however, the underlying mechanism remains to be investigated. It is widely accepted that certain noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), can regulate endothelial cell behavior, including their involvement in angiogenesis. Therefore, we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells (HUVECs).Methods:We evaluated VEGF-A messenger RNA (mRNA) and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis, we measured expression of the miRNAs miR-210, miR-21, and miR-1, as well as that of the lncRNAs growth arrest-specific transcript 5 (GAS5), maternally expressed 3 (MEG3), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HUVECs exposed to ISO. Furthermore, to ascertain its importance in ISO-mediated angiogenesis, we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs. All statistical analyses were performed using SPSS 16.0 software. Intergroup comparisons were carried out by one-way analysis of variance.Results:VEGF-A mRNA levels were elevated in the ISO group (1.57 ± 0.09) compared to those in the control group (P < 0.01). Moreover, concentrations of VEGF-A in culture supernatants significantly differed between the control (113.00 ± 19.21 pg/ml) and ISO groups (287.00 ± 20.27 pg/ml; P < 0.01). Expression of miR-1, miR-21, and miR-210 was higher (3.89 ± 0.44, 2.87 ± 087, and 3.33 ± 1.31, respectively) in ISO-treated cells than that in controls (P < 0.01), whereas that of GAS5 and MEG3 (0.22 ± 0.10 and 0.58 ± 0.16, respectively) was lower as a result of ISO administration (P < 0.05). There was no significant difference in the expression of MALAT1 between the groups. Interestingly, miR-210 overexpression heightened the levels of VEGF-A and miR-21 (5.87 ± 1.24 and 2.74 ± 1.15, respectively; P < 0.01) and reduced those of GAS5 and MEG3 (0.19 ± 0.01 and 0.09 ± 0.05, respectively; P < 0.01).Conclusions:ISO-mediated angiogenesis was associated with altered expression of miR-210, miR-21, and the lncRNAs GAS5 and MEG3. The effects of miR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO, indicating that it might play an important role in ISO-mediated angiogenesis.

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The Long Noncoding RNA MEG3 Is Downregulated and Inversely Associated with VEGF Levels in Osteoarthritis

Cited by 117 publications

References 20 publications

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

Integrated analysis of key mRNAs and lncRNAs in osteoarthritis

MicroRNA-210 Plays a Critical Role in the Angiogenic Effect of Isoprenaline on Human Umbilical Vein Endothelial Cells via Regulation of Noncoding RNAs

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