MiR-499a-5p suppresses apoptosis of human nucleus pulposus cells and degradation of their extracellular matrix by targeting SOX4

Sun, Jingchuan; Zheng, Bing; Sun, Rongxin; Meng, Yake; Wang, Shunmin; Yang, Haisong; Chen, Yu; Guo, Yongfei

doi:10.1016/j.biopha.2019.108652

Cited by 38 publications

(36 citation statements)

References 26 publications

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“…Consistently, miR-499a-5p expression has been shown to be remarkedly decreased after myocardial I/R injury (Liu et al 2019). Similarly, miR-499a-5p may attenuate TNF-α-induced human nucleus pulposus cell apoptosis (Sun et al 2019). These data indicated that miR-499a-5p suppressed the cerebral I/R injury might by decreasing MCAO-induced apoptosis.…”

Section: Discussionmentioning

confidence: 58%

“…Apoptosis usually occupies a crucial role in the pathogenesis of ischemic brain injury and the subsequent reperfusion damage (He et al 2016;Machado et al 2009). Similar to miR-499a-5p-induced suppression of apoptosis, miR-499a-5p could suppress the apoptosis of human nucleus pulposus cells and degradation of their extracellular matrix by targeting SOX4 (Sun et al 2019). Downregulation of CD38 by miR-499a-5p signi cantly decreased the apoptosis and the LDH activity of H9C2 cells under hypoxia-reoxygenation conditions (Zhao et al 2020).…”

Section: Discussionmentioning

confidence: 89%

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Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4

Shan

Chen

et al. 2021

Cell Mol Neurobiol

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MiR-499a-5p was signi cantly down-regulated in degenerative tissues and correlated with apoptosis.Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found the plasma levels of miR-499a-5p were signi cantly down-regulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay and ow cytometry analysis. These ndings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 89%

Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4

Shan

Chen

et al. 2021

Cell Mol Neurobiol

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“…For instance, downregulated miR-155 was suggested triggering the Fas-mediated apoptosis by disinhibiting FADD and CASP-3 in NP cells [18]. Similarly, the expression of miR-21 [36], miR-499a-5p [40], miR-486-5p [46], miR-125a [51], miR-145 [56], and miR-573 [57] are decreased in IDD, which act as apoptosis inhibitors via binding to the 3′UTRs of mRNAs of PTEN, SOX4, FOXO1, TP53INP1, ADAM17, and Bax, respectively. In contrast to these findings, miRNAs such as miR-27a [39], miR-494 [41,42], miR-30d [43], miR-222-3p [44], miR-15a [45], miR-143 [49], miR-532 [50], miR-138-5p [55] in NP cells, miR-106a-5p [8] in AF cells, and miR-34a [7] and miR-221 [52] in CEP cells, display potential proapoptotic effects in IDD, via inhibiting the expression of downstream hub proteins in several pathways.…”

Section: The Roles Of Mirnas In Ivd Cell Apoptosismentioning

confidence: 96%

“…Wang et al discovered that miR-21 is upregulated in IDD tissues and positively correlated with the degradation grade, which indicates miR-21 cannot only inhibit NP cell apoptosis and promote proliferation as mentioned above, but also promote ECM degradation through repressing the PTEN/AKT/mTOR signaling pathway [38]. SRYrelated high-mobility group box (SOX)-4 and SOX9 are respectively targeting molecules of miR-499a-5p [40], miR-494 [41], and miR30d [43], by repressing the apoptosis of NP cells and ECM degradation.…”

Section: The Roles Of Mirnas In Ecm Degradation and Inflammationmentioning

confidence: 99%

Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

Guo

Wan

et al. 2020

Arthritis Res Ther

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Intervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

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“…Grouping and transfection of NP cells NP cells were divided into 6 groups: Blank group (NP cells without any treatment), TNF-α group (NP cells treated with 20 ng/mL TNF-α for 12 h 16 ), TNF-α + miR-NC group (NP cells transfected with miRNA NC prior to TNF-α treatment), TNF-α + miR-195 inhibitors group (NP cells transfected with miR-195 inhibitors prior to TNF-α treatment), TNF-α + siBcl-2 group (NP cells transfected with Bcl-2 siRNA prior to TNF-α treatment) and TNF-α + miR-195 inhibitors + siBcl-2 group (NP cells co-transfected with miR-195 inhibitors and Bcl-2 siRNA prior to TNF-α treatment). MiRNA negative control (NC), miR-195 inhibitors and Bcl-2 siRNA were all purchased from Shanghai Genechem Co., Ltd.…”

Section: Dual-luciferase Reporter Gene Assaymentioning

confidence: 99%

Expression of miR-195 and its target gene Bcl-2 in human intervertebral disc degeneration and their effects on nucleus pulposus cell apoptosis

Lin

Zheng

Zhang

et al. 2021

Preprint

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Objective: To investigate the expression of miR-195 and its target gene Bcl-2 in intervertebral disc degeneration (IVDD) and its effect on nucleus pulposus (NP) cell apoptosis.Methods: The expressions of miR-195 and Bcl-2 in NP tissues of IVDD patients were quantified by qRT-PCR and Western blotting, respectively. NP cells were divided into Blank group, TNF-α group, TNF-α + miR-NC group, TNF-α + siBcl-2 group, and TNF-α + miR-195 inhibitors + siBcl-2 group. Cell proliferation was detected by MTT assay, cell apoptosis evaluated by flow cytometry, and mitochondrial membrane potential (MMP) tested by JC-1 staining. Moreover, the function of miR-132 on IVDD in vivo was investigated using a puncture-induced IVDD rat model.Results: IVDD patients had significantly increased miR-195 expression and decreased Bcl-2 protein expression in NP tissues. The expression of miR-195 was negatively correlated with the expression of Bcl-2 in IVDD patients. Dual-luciferase reporter gene assay indicated that Bcl-2 was a target gene of miR-195. In comparison with Blank group, TNF-α group showed decreased cell proliferation and MMP, increased cell apoptosis, up-regulated expression of miR-195, Bax and cleaved caspase 3, and down-regulated Bcl-2 protein, while these changes were attenuated by miR-195 inhibitors. Additionally, siBcl-2 can reverse the protective effect of miR-195 inhibitors on TNF-α-induced NP cells. Besides, inhibition of miR-195 alleviated IVDD degeneration and NP cell apoptosis in the rat model.Conclusion: MiR-195 was significantly up-regulated in NP tissues of IVDD patients, and inhibition of miR-195 could protect human NP cells from TNF-α-induced apoptosis via upregulation of Bcl-2.

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MiR-499a-5p suppresses apoptosis of human nucleus pulposus cells and degradation of their extracellular matrix by targeting SOX4

Cited by 38 publications

References 26 publications

Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4

Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4

Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

Expression of miR-195 and its target gene Bcl-2 in human intervertebral disc degeneration and their effects on nucleus pulposus cell apoptosis

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