CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

Xie, Lin; Huang, Weibo; Fang, Zhenhua; Ding, Fan; Zou, Fei; Ma, Xiaosheng; Tao, Jie; Guo, Jingkang; Xia, Xinlei; Wang, Hongli; Yu, Zuochong; Lu, Feizhou; Jiang, Jianyuan

doi:10.1038/s41419-019-1978-2

Cited by 109 publications

(125 citation statements)

References 58 publications

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“…Mitochondrial dysfunction causes cell/organ injury through several mechanisms, including diminished cellular energy status (low cellular ATP level, energy stress) and enhanced production of reactive oxygen species (ROS). Furthermore, mitochondrial damage is associated with the release of several apoptosis-activated factors, leading to programmed cell death [163]. Disturbances in ionic balance, particularly an increase in mitochondrial and cytoplasmic Ca 2+ , stimulates mitochondrial permeability transition (PT) accompanied by the opening of non-selective channels known as the PT pores (PTP) that allow free movement of ions and other solutes with a molecular mass <1.5 kDa across the inner mitochondria membrane (IMM) [4].…”

Section: Mitophagymentioning

confidence: 99%

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

Zhou

Toan

2020

Biomolecules

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Mitochondria are key regulators of cell fate through controlling ATP generation and releasing pro-apoptotic factors. Cardiac ischemia/reperfusion (I/R) injury to the coronary microcirculation has manifestations ranging in severity from reversible edema to interstitial hemorrhage. A number of mechanisms have been proposed to explain the cardiac microvascular I/R injury including edema, impaired vasomotion, coronary microembolization, and capillary destruction. In contrast to their role in cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. It is clear that abnormal mitochondrial signatures, including mitochondrial oxidative stress, mitochondrial fission, mitochondrial fusion, and mitophagy, play a substantial role in endothelial cell function. While the pathogenic role of each of these mitochondrial alterations in the endothelial cells I/R injury remains complex, profiling of mitochondrial oxidative stress and mitochondrial dynamics in endothelial cell dysfunction may offer promising potential targets in the search for novel diagnostics and therapeutics in cardiac microvascular I/R injury. The objective of this review is to discuss the role of mitochondrial oxidative stress on cardiac microvascular endothelial cells dysfunction. Mitochondrial dynamics, including mitochondrial fission and fusion, are critically discussed to understand their roles in endothelial cell survival. Finally, mitophagy, as a degradative mechanism for damaged mitochondria, is summarized to figure out its contribution to the progression of microvascular I/R injury.

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Section: Mitophagymentioning

confidence: 99%

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

Zhou

Toan

2020

Biomolecules

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“…A large of studies shown that the degeneration mainly displays as a large number of the nucleus pulposus cell apoptosis and thus nucleus pulposus cells apoptosis plays a crucial role in IVDD [7,8]. TNF-α is a key proinflammatory cytokine and could induce the apoptosis of nucleus pulposus cells [9]. Thus, TNF-α was commonly administrated as the model of IVDD [10].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

et al. 2020

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Background: Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. Methods: First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. Results: There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly upregulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly downregulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80-87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P < 0.05). Conclusion: These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

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“…SirT1-small interfering (si)rna inhibits nPc apoptosis and senescence. Moreover, this effect is suppressed by circ-ercc2 and mir-182-5p inhibitor, suggesting that circercc2 exerts a protective effect on nPcs that is dependent on mir-182-5p (17).…”

Section: Specificroles Of Circrna In Iddmentioning

confidence: 96%

“…Functional analyses also suggested that circ-ercc2 modulated tert-butyl hydroperoxide-induced nPc apoptosis (through caSP-3, caSP-7 and caSP-9), mitophagy (through PTen-induced kinase 1, parkin, p62, and lc3ii/i) and ecM structure (MMP13 and col2) in vitro and in vivo (17). Fluorescence in situ hybridization and dual-luciferase assays demonstrated that circ-ercc2 could bind to mir-182-5p (17).…”

Section: Specificroles Of Circrna In Iddmentioning

confidence: 97%

“…matrix metalloproteinases (MMPs), disintegrin and adaM metallopeptidases with thrombospondin type 1 motifs (adaMTSs), interleukin (il)-1β, tumor necrosis factor-α (TnF-α) and a number of proapoptotic proteins (4,(9)(10)(11). Previous studies have suggested that ncrnas, including micrornas (mirnas/mirs) and circular rnas (circrnas), serve a crucial role in the occurrence and progression of idd (12)(13)(14)(15)(16)(17). in particular, circrnas mediate nP cell (nPc) apoptosis and regulate the expression of inflammatory cytokines, MMP, adaMTS, various apoptosis-related proteins and key components of the ecM, such as col2 and acan, which serve a role in the pathogenesis of idd (12)(13)(14)(15)(16)(17).…”

Section: Emerging Role Of Circular Rna In Intervertebral Disc Degenermentioning

confidence: 99%

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Emerging role of circular RNA in intervertebral disc degeneration: Knowns and unknowns (Review)

Zhou

Peng

et al. 2020

Mol Med Rep

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lower back pain (lBP) is one of the predominant factors contributing to dyskinesia and remains a serious social and economic burden worldwide. intervertebral disc degeneration (idd) is the leading cause of lBP; the existing idd treatments cannot completely prevent idd. circular rnas (circrnas) are non-coding rnas resulting from back-splicing with unique structural characteristics and functions. accumulating evidence suggests that circrnas are involved in the pathological process of idd and modulate a range of idd-related genes or proteins. However, the underlying circrna-mediated regulatory mechanisms remain poorly understood. The aim of the present review is to describe the current understanding of circRNA characteristics, classification, biogenesis and function in relation to its specific roles in idd. additionally, the limitations on the current knowledge in the field and the future direction of IDD-related research are also discussed. Contents 1. introduction 2. characteristics 3. Classifications 4. Biogenesis and functions 5. Specific roles of circRNA in IDD 6. current limitations and future directions 7. conclusions

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CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

Cited by 109 publications

References 58 publications

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

Emerging role of circular RNA in intervertebral disc degeneration: Knowns and unknowns (Review)

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