MiR-138-5p promotes TNF-α-induced apoptosis in human intervertebral disc degeneration by targeting SIRT1 through PTEN/PI3K/Akt signaling

Wang, Bing; Wang, Dongqi; Yan, Tao; Yuan, Huijun

doi:10.1016/j.yexcr.2016.05.011

Cited by 81 publications

(65 citation statements)

References 24 publications

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“…The findings suggested that miR-148a was significantly downregulated in IDD patients compared with the healthy controls, as well as in the LPS-stimulated NP cells compared with non-stimulated cells. Similar to these results, previous studies on miRNA expression in degenerative discs have reported that numerous miRNAs are abnormally expressed in IDD (22)(23)(24)(25). To investigate the underlying mechanism of the role of miR-148a in IDD, a stable miR-148a-overexpression/underexpression human NP cell line was established by transfection with miR-148a mimic/inhibitor and an IDD cell model was established by LPS stimulation.…”

Section: Discussionsupporting

confidence: 80%

miR‑148a inhibits pro‑inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway

Tang

Chen

et al. 2018

Exp Ther Med

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Section: Discussionsupporting

confidence: 80%

miR‑148a inhibits pro‑inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway

Tang

Chen

et al. 2018

Exp Ther Med

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“…MiR-138 is expressed at levels comparable to BART5 and let-7 in Jijoye cells [18], but our HITS-CLIP data do not overlap with this site, and no others have validated its direct regulation of CASP3. Consistent with this is the recent finding that miR-138 inhibits TNF-α-induced apoptosis in the human intervertebral disc, where an inhibitor of miR-138 dramatically suppressed the expression of cleaved CASP3 [34]. …”

Section: Discussionsupporting

confidence: 76%

Epstein-Barr viral microRNAs target caspase 3

Harold

Cox

Riley

2016

Virol J

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The Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that transforms B cells and causes several malignancies including Burkitt’s lymphoma. EBV differentially expresses at least 49 mature microRNAs (miRNAs) during latency in various infected epithelial and B cells. Recent high-throughput studies and functional assays have begun to reveal the function of the EBV miRNAs suggesting roles in latency, cell cycle control, and apoptosis. In particular, the central executioner of apoptosis, Caspase 3 (CASP3), was proposed as a target of select EBV miRNAs. However, whether CASP3 is truly a target of EBV miRNAs, and if so, which specific miRNAs target CASP3 is still under debate. Based on previously published high-throughput biochemical data and a bioinformatic analysis of the entire CASP3 3′-UTR, we identified 12 EBV miRNAs that have one or more seed binding sites in the CASP3 3′-UTR. We individually tested all 12 miRNAs for repression of CASP3 in luciferase reporter assays, and nine showed statistically significant (P < 0.001) repression of a full-length CASP3 reporter. Further, three EBV miRNAs, including BART22, exhibited repression of endogenous CASP3 protein. These data confirm that CASP3 is a direct target of specific EBV BART miRNAs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0602-7) contains supplementary material, which is available to authorized users.

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“…The Shh-signal pathway is one of the Hedgehog pathways that regulate the development and differentiation of vertebrate entoderm, which is a highly conservative morphogenesis pathway of the medial axis organ development existing in both Drosophila melanogaster and vertebrate (10–13). Membrane proteins Ptch and Smo control Shh-signal transmission towards the cell, and receptor Ptch negatively regulates the Shh-signaling pathway (14–16).…”

Section: Discussionmentioning

confidence: 99%

Research on the function and related mechanism of P27 gene in the intervertebral disc degeneration of mice

Liu

Wang

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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This study aims to investigate the function and related mechanism of P27 gene in intervertebral disc (IVD) degeneration of mice. X-ray, immunohistochemical staining, and alkaline phosphatase (ALP) histochemical staining were used to analyze the phenotypic difference of the intervertebral discs of 4-week-old mice with P27 gene knockout (P27−/−) and wild-type (WT) mice in the same brood. Protein in the intervertebral disc was extracted and western blot analysis was employed to detect the changes in the expression of related molecules in the Shh-signal pathways, including Shh, Patched, Smoothened and Gli2. As a result, the ALP histochemical staining revealed that the ALP-positive area of mice in the P27−/− group was obviously increased compared to the 4-week-old mice of the same brood in the WT group. In addition, the Col-I immunohistochemical staining showed that the Col-I-positive area of mice in the P27−/− group was significantly increased compared to mice in the WT group. Furthermore, Smo-positive cell rate of mice in the P27−/− group was apparently increased compared to mice in the WT group. Western blot analysis revealed that in terms of changes of protein expression levels of Shh, Patched, Smoothened and Gli2 in the intervertebral disc, protein expression levels of Shh, Patched, Smoothened and Gli2 of mice in the P27−/− group were significantly increased compared to those of mice in the WT group. The results show that P27 deficiency activates the expression of Shh-signal pathway and promotes the proliferation of osteoblast, thus, playing a role in promoting IVD degeneration, which provides a scientific and reliable experimental basis for the treatment of the IVD degeneration-related diseases in clinical practice.

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MiR-138-5p promotes TNF-α-induced apoptosis in human intervertebral disc degeneration by targeting SIRT1 through PTEN/PI3K/Akt signaling

Cited by 81 publications

References 24 publications

miR‑148a inhibits pro‑inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway

miR‑148a inhibits pro‑inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway

Epstein-Barr viral microRNAs target caspase 3

Research on the function and related mechanism of P27 gene in the intervertebral disc degeneration of mice

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