Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

Zhang, Shuai; Sun, Yong; Yuan, Zhiqiang; Liu, Ying; Li, Xiaolu; Gong, Zhenyu; Peng, Yizhi

doi:10.5483/bmbrep.2013.46.1.037

Cited by 14 publications

(13 citation statements)

References 28 publications

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“…Moreover, Hsp90β inhibitors can inhibit the migration and invasion of glioma cells and inhibit the secretion of vascular endothelial growth factor [28]. In addition, other studies clarified that Hsp90 β inhibits the apoptosis of intestinal cells by activating Akt pathway [51]. The above findings are consistent with our findings.…”

Section: Discussionsupporting

confidence: 92%

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Zhao

Liu

et al. 2019

J Exp Clin Cancer Res

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BackgroundRNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs).MethodsThe expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student’s t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis.ResultsThe expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway.ConclusionsMOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0990-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Zhao

Liu

et al. 2019

J Exp Clin Cancer Res

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“…HSPs are well known to respond to hypoxia via HSFs by preventing the dephosphorylation of Akt (Zhang et al . ). Irs1 (upstream of PI3K–Akt), which can be depressed by NO signalling in hypoxia (Sugita et al .…”

Section: Discussionmentioning

confidence: 97%

Transcriptomic analysis identifies a role of PI3K–Akt signalling in the responses of skeletal muscle to acute hypoxia in vivo

Zhang

Powell

Zambon

et al. 2017

The Journal of Physiology

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The effects of acute hypoxia have been widely studied, but there are few studies of transcriptional responses to hours of hypoxia in vivo, especially in hypoxia-tolerant tissues like skeletal muscles. We used RNA-seq to analyse gene expression in plantaris muscles while monitoring respiration, arterial blood gases, and blood glucose in mice exposed to 8% O for 2 or 6 h. Rapid decreases in blood gases and a slower reduction in blood glucose suggest stress, which was accompanied by widespread changes in gene expression. Early down-regulation of genes associated with the extracellular matrix was followed by a shift to genes associated with the nuclear lumen. Most of the early down-regulated genes had mRNA half-lives longer than 2 h, suggesting a role for post-transcriptional regulation. These transcriptional changes were enriched in signalling pathways in which the PI3K-Akt signalling pathway was identified as a hub. Our analyses indicated that gene targets of PI3K-Akt but not HIF were enriched in early transcriptional responses to hypoxia. Among the PI3K-Akt targets, 75% could be explained by a deactivation of adenylate-uridylate-rich element (ARE)-binding protein BRF1, a target of PI3K-Akt. Consistent decreases in the phosphorylation of Akt and BRF1 were experimentally confirmed following 2 h of hypoxia. These results suggest that the PI3K-Akt signalling pathway might play a role in responses induced by acute hypoxia in skeletal muscles, partially through the dephosphorylation of ARE-binding protein BRF1.

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“…18 Some previous animal studies indicate that HSP90 may have a dual role and increase inflammation in some conditions, while being protective and down-regulating inflammation in other conditions. [19][20][21] Fatigue has previously been an overlooked and ignored phenomenon in IBD but is increasingly recognised as one of the major problems for many patients. Clinically significant fatigue affects roughly 50% of patients at the time of diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn’s disease

et al. 2019

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Heat-shock proteins (HSPs) are evolutionarily conserved proteins with important cellular homeostasis functions during harmful conditions, including inflammation. Some HSPs are secreted extracellularly and act on distant cells by down-regulating inflammation and increasing cellular stress defence mechanisms. HSP90α has been postulated to signal fatigue in chronic inflammation. We investigated whether HSP90α is associated with fatigue in patients with Crohn’s disease. Fifty-three patients with newly diagnosed Crohn’s disease were included in a cross-sectional study. Data on demographics and disease distribution were obtained. Fatigue was measured by the fatigue visual analogue scale (fVAS). Disease activity was assessed by the Simple Endoscopic Score for Crohn’s disease and Harvey Bradshaw Index. C-reactive protein, faecal calprotectin and HSP90α were also measured. The median fVAS score was 52 mm, indicating significant fatigue. HSP90α scores correlated significantly with fVAS ( r = 0.31, P = 0.03). In a multivariate regression model, HSP90α was the only significant contributor to fVAS scores (β = 0.31, P = 0.03). When patients were dichotomised into groups with high and low HSP90α concentrations, significantly higher fVAS scores were demonstrated in the group with high HSP90α ( M = 62.4, confidence interval 53.0–71.8 vs. 43.3, 31.6–55.0; P = 0.01). Thus, HSP90α may contribute to fatigue generation and/or modulation in patients with Crohn’s disease.

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Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

Cited by 14 publications

References 28 publications

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Transcriptomic analysis identifies a role of PI3K–Akt signalling in the responses of skeletal muscle to acute hypoxia in vivo

Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn’s disease

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