MST1 suppresses viability and promotes apoptosis of glioma cells via upregulating SIRT6 expression

Zhu, Dapeng; Sun, Chao; Xiang, Qing

doi:10.31083/j.jin.2019.02.122

Cited by 14 publications

(6 citation statements)

References 37 publications

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“…MST1 expression can also be directly repressed by miR-130b, which can target the MST1-adaptor protein SAV1 [52]. Moreover, miR-130b was found to be upregulated in both GBM tissues and cell lines, which is concordant with MST1 downregulation reported by Zhu et al [53]. Functional MST1 overexpression has been marked by the induction of SIRT6 (Sirtuin 6), reducing glioma cell viability and colony formation and promoting apoptosis through the activation of FOXO3a transcription factor.…”

Section: Mst1/2supporting

confidence: 78%

Hippo Signaling Pathway in Gliomas

Masliantsev

Karayan‐Tapon

Guichet

2021

Cells

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The Hippo signaling pathway is a highly conserved pathway involved in tissue development and regeneration that controls organ size through the regulation of cell proliferation and apoptosis. The core Hippo pathway is composed of a block of kinases, MST1/2 (Mammalian STE20-like protein kinase 1/2) and LATS1/2 (Large tumor suppressor 1/2), which inhibits nuclear translocation of YAP/TAZ (Yes-Associated Protein 1/Transcriptional co-activator with PDZ-binding motif) and its downstream association with the TEAD (TEA domain) family of transcription factors. This pathway was recently shown to be involved in tumorigenesis and metastasis in several cancers such as lung, breast, or colorectal cancers but is still poorly investigated in brain tumors. Gliomas are the most common and the most lethal primary brain tumors representing about 80% of malignant central nervous system neoplasms. Despite intensive clinical protocol, the prognosis for patients remains very poor due to systematic relapse and treatment failure. Growing evidence demonstrating the role of Hippo signaling in cancer biology and the lack of efficient treatments for malignant gliomas support the idea that this pathway could represent a potential target paving the way for alternative therapeutics. Based on recent advances in the Hippo pathway deciphering, the main goal of this review is to highlight the role of this pathway in gliomas by a state-of-the-art synthesis.

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Section: Mst1/2supporting

confidence: 78%

Hippo Signaling Pathway in Gliomas

Masliantsev

Karayan‐Tapon

Guichet

2021

Cells

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“…Apoptosis is one of the major mechanisms underlying the death of RGCs with retinal I/R injury and a common pathway of RGC degeneration [ 42 ]. Apoptosis is a type of programmed cell death cascade caused by a large number of death signal receptors under certain stimulus factors [ 43 , 44 ]. In our study, we observed that apoptotic cells in the model group were more numerous than those in the control group, and this apoptosis was observably attenuated by ligustrazine in RGCs after I/R injury.…”

Section: Resultsmentioning

confidence: 99%

Ligustrazine induces viability, suppresses apoptosis and autophagy of retinal ganglion cells with ischemia/reperfusion injury through the PI3K/Akt/mTOR signaling pathway

Wang

et al. 2021

Bioengineered

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Ligustrazine, an alkaloid monomer extracted from Chuanxiong Rhizoma, has the function of protecting nerve cells. However, the effect and mechanism of ligustrazine on retinal ischemia/ reperfusion (I/R) injury still need to be clarified. In our study, retinal ganglion cells (RGC-5) were used to establish a retinal I/R injury model by anaerobic cultivation. Cell viability, autophagy, and apoptosis were evaluated by cell counting kit 8 assay, transmission electron microscopy, and TUNEL staining after treatment with ligustrazine, PI3K inhibitor Ly294002, and/or mTOR inhibitor rapamycin, respectively. Besides, the levels of PI3K/Akt/mTOR pathway and autophagy-related proteins were determined by western blot. Moreover, one-way ANOVA was adopted for intergroup comparisons of measurement data. Our results demonstrated that low-concentration ligustrazine significantly enhanced cell viability and suppressed cell autophagy and apoptosis of RGC-5 cells after I/R injury, suggesting the protective effect of low-concentration ligustrazine on retinal I/R injury. Moreover, the alleviating effect of ligustrazine on RGC-5 with retinal I/R injury was mechanistically associated with the activation of the PI3K/Akt/mTOR pathway. In conclusion, low-concentration ligustrazine has a significant protective effect on RGC-5 cells with retinal I/R injury by activating the PI3K/Akt/mTOR pathway.

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“…The current study confirms the carcinogenic effects of SIRT6 in glioma. There is evidence that SIRT6 is regulated by MST1 and miR-33a and can inhibit the activity of glioma cells (Chang et al, 2017;Zhu et al, 2019). In conclusion, these findings suggest that sirtuin protein is related to glioma onset and progression, suggesting these proteins as potential biomarkers for evaluating prognosis of the glioma.…”

Section: Discussionmentioning

confidence: 70%

Constructing a signature based on the SIRT family to help the prognosis and treatment sensitivity in glioma patients

et al. 2022

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Enzymes of the silent information regulator (SIRT) family exert crucial roles in basic cellular physiological processes including apoptosis, metabolism, ageing, and cell cycle progression. They critically contribute to promoting or inhibiting cancers such as glioma. In the present study, a new gene signature of this family was identified for use in risk assessment and stratification of glioma patients. To this end, the transcriptome and relevant clinical records of patients diagnosed with glioma were obtained from the Cancer Genomic Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LASSO regression and multivariate Cox analyses were used to establish the signature. Using Kaplan–Meier analyses, overall survival (OS) was assessed and compared between a training and an external test datasets which showed lower OS in patients with high risk of glioma compared to those with low risk. Further, ROC curve analyses indicated that the SIRT-based signature had the desired accuracy and universality for evaluating the prognosis of glioma patients. Using univariate and multivariate Cox regression analyses, the SIRT-based signature was confirmed as an independent prognostic factor applicable to subjects in the TCGA and CGGA databases. We also developed an OS nomogram including gender, age, risk score, pathological grade, and IDH status for clinical decision-making purposes. ssGSEA analysis showed a higher score for various immune subgroups (e.g., CD8+ T cells, DC, and TIL) in samples from high-risk patients, compared to those of low-risk ones. qPCR and western blotting confirmed the dysregulated expression of SIRTs in gliomas. Taken together, we developed a new signature on the basis of five SIRT family genes, which can help accurately predict OS of glioma patients. In addition, the findings of the present study suggest that this characteristic is associated with differences in immune status and infiltration levels of various immune cells in the tumor microenvironment.

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MST1 suppresses viability and promotes apoptosis of glioma cells via upregulating SIRT6 expression

Cited by 14 publications

References 37 publications

Hippo Signaling Pathway in Gliomas

Hippo Signaling Pathway in Gliomas

Ligustrazine induces viability, suppresses apoptosis and autophagy of retinal ganglion cells with ischemia/reperfusion injury through the PI3K/Akt/mTOR signaling pathway

Constructing a signature based on the SIRT family to help the prognosis and treatment sensitivity in glioma patients

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