The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis

Xu, Jin; Xu, Yaozeng

doi:10.1186/s13578-017-0195-x

Cited by 88 publications

(106 citation statements)

References 32 publications

(48 reference statements)

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“…There are accumulating data showing that lncRNAs play an important role in OA by regulating chondrocyte proliferation and apoptosis. For example, the expression of lncRNA MEG3 was downregulated, and miR‐16 was upregulated in OA, MEG3‐miR‐16 signaling pathway mediates osteoarthritis progression through targeting SMAD7 . In addition, Jiang et al .…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

Lü¹,

Zhou

2020

Pathology International

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Previous studies demonstrated that dysregulation of G protein‐coupled receptor 120 (GPR120) plays a protective role in osteoarthritis (OA). However, the mechanism underlying how GPR120 is downregulated remains largely unknown. In the present study, we evaluated whether GPR120 is regulated by microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Our results show that GPR120 was negatively regulated by miR‐15b‐5p through targeting 3′ untranslated region (3′UTR), and that miR‐15b‐5p was negatively regulated by LINC00662. Further luciferase assay shows that LINC00662‐miR‐15b‐5p signaling pathway contributed the regulation of GPR120 expression. Functionally, the decreased of LINC00662 caused increased miR‐15b‐5p, thereby leading to decreased GPR120. The decreased GPR120 then contributes to increased expression of inflammatory factors including tumor necrosis factor α (TNF‐α), interleukin (IL)‐6 and IL‐8, cell apoptosis, and decreased apoptosis‐related protein levels including cleaved caspase‐3, cleaved caspase‐9, and Bax in cultured rat chondrocytes. In summary, the present study shows that LINC00662‐miR‐15b‐5p signaling pathway is involved in the regulation of GPR120, thereby contributing to arthritis.

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Section: Discussionmentioning

confidence: 99%

“…Importantly, various studies have shown that lncRNAs exerted their regulatory effect through microRNAs (miRNAs). Xu et al . demonstrated that lncRNA MEG3 was downregulated and miR‐16 was upregulated in cartilage tissues of rat OA model, and this signaling pathway is involved in the initiation and development of OA.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

Lü¹,

Zhou

2020

Pathology International

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“…OA is a heterogeneous disease affects all synovial joints, such as spine, hips or knees. OA can also be regarded as a degenerative disease as the main pathological features of OA are progressive articular cartilage degeneration . Ageing is the major risk factor for OA and other factors including obesity and heredity also contribute to the development of OA .…”

Section: Discussionmentioning

confidence: 99%

LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

Lü

et al. 2019

J Cellular Molecular Medi

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Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non‐coding (lncRNAs) prostate androgen‐regulated transcript‐1 (PART‐1) on chondrocytes apoptosis. In the present study, the PART‐1 expression level was down‐regulated in the OA cartilages. Silence of PART‐1 decreased the cell viability and promoted chondrocytes apoptosis. Overexpression of PART‐1 could reverse the effects induced by interleukin 1β (IL‐1β) stimulation, thus slowing down the apoptosis rate. MiR‐590‐3p was found to be the potential target, and RNA immunoprecipitation and luciferase activity assay confirmed the binding between PART‐1 and miR‐590‐3p. Moreover, miR‐590‐3p was down‐regulated by PART‐1 and was negatively associated with PART‐1. Transforming growth factor‐beta receptor type 2 (TGFBR2) was positively associated with PART‐1. Down‐regulation of PART‐1 decreased cell viability and induced cell apoptosis, which was partially reversed by miR‐590‐3p silence or TGFBR2 overexpression; while overexpression of PART‐1 increased the cell viability and decreased the caspase 3 activity and apoptotic rates, and the effects were partially attenuated by miR‐590‐3p overexpression or silence of TGFBR2 in IL‐1β‐stimulated chondrocytes. Knock‐down of PART‐1 down‐regulated both Smad3 and p‐Smad3 protein levels, which was reversed by miR‐590‐3p inhibition or TGFBR2 overexpression. Smad3 expression level was lower in the OA group than that in the normal group and was positively associated with the PART‐1 expression level. Collectively, the study revealed that lncRNA PART‐1 regulates the apoptosis of chondrocytes in OA by acting as a sponge for miR‐590‐3p, which subsequently regulates TGFBR2/Smad3 signalling.

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“…lncRNAs are also involved in the pathogenesis of OA. Several lines of evidence have indicated that lncRNAs, such as H19, 11 MEG3, 6 F I G U R E 4 MiR-130a decreased the relative luciferase activity by directly binding with the 3′UTR of lncRNA-CIR and Bim. A, Schematic diagram of the interaction of miR-130a and Bim; B, relative luciferase activity; C, schematic diagram of the interaction of miR-130a and lncRNA-CIR; D, relative luciferase activity.…”

Section: Effect Of Overexpression Of Mir-130a On Ros Inflammationmentioning

confidence: 99%

lncRNA‐CIR regulates cell apoptosis of chondrocytes in osteoarthritis

Luo

Huang

2018

J of Cellular Biochemistry

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Background and Objectives Osteoarthritis (OA) is a complex chronic degenerative joint disease involving oxidative stress, inflammation, and apoptosis of chondrocytes. As decoys of micro RNAs, long non‐coding RNAs (lncRNAs) play important roles in various biological processes. This study was designed to investigate the interactions between lncRNA‐CIR, chondrocyte apoptosis, and the molecular mechanisms underlying OA. Methods Primary cultured chondrocytes were stressed using H2O2, IL‐1β, or TNF‐ɑ to simulate conditions found in OA. Quantitative real‐time PCR was performed to detect miR‐130a, lncRNA‐CIR, and Bim mRNA expression levels. Western blot analysis was used to detect Bim protein expression levels. Reactive oxygen species (ROS) levels were assayed by detecting the fluorescent signal of 2′,7′‐dichlorodihydrofluorescein diacetate (DCFH‐DA). Cell apoptosis was measured with combined staining of PI and DAPI. lncRNA‐CIR knockdown and miR‐130a over‐expression or inhibition were performed using small interfering RNAs, and miR‐130 mimics or inhibitors, respectively. Results lncRNA‐CIR is significantly upregulated in OA patients, accompanied by downregulation of miR‐130a and upregulation of Bim. Bio‐informatics analysis predicted miR‐130a as a target of both lncRNA‐CIR and Bim. While lncRNA‐CIR knockdown significantly increased the expression of Bim, miR‐130a significantly suppressed Bim expression, with accompanying increases of ROS level, inflammatory mediator release, cell apoptosis, and relative luciferase activity. Conclusions The present findings demonstrated that the lncRNA‐CIR/miR‐130a/Bim axis is involved in oxidative stress‐related apoptosis of chondrocytes in OA.

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The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis

Cited by 88 publications

References 32 publications

Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

lncRNA‐CIR regulates cell apoptosis of chondrocytes in osteoarthritis

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