Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

Yan, Huixin; Qiu, Chengmin; Sun, Weiwei; Gu, Minmin; Xiao, Feng; Zou, Jue; Zhang, Li

doi:10.3892/or.2018.6252

Cited by 67 publications

(71 citation statements)

References 53 publications

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“…The similar results could also be observed in the study of Zhou and his colleagues [28]. Moreover, Yan showed that YAP acted as a tumor promoter in gastric cancer, and involved in the survival and migration of GC cells through the activation of the SIRT1/Mfn2/mitochondrial autophagy axis [29]. However, there are still inconsistent results published.…”

Section: Discussionsupporting

confidence: 78%

Association of Elevated Yes-Associated Protein Expression with Gastric Cancer and Its Clinicopathological Features: A Meta-Analysis

Peng¹,

Yuan²,

Duan³

et al. 2020

JBM

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Objectives: To evaluate the difference of YAP-positive expression between GC and adjacent tissues, as well as the association of elevated YAP expression with clinicopathological features of GC. Methods: PubMed, Embase, Web of Science databases and the Chinese National Knowledge Infrastructure (CNKI) were searched from inception up to December 2018. The pooled ORs and corresponding 95% CIs were used to assess the strength of association. The heterogeneity among eligible studies was evaluated by the Q-test and I 2 values. The sensitivity analysis was performed by sequential omission of individual studies. Moreover, Begg's test and Egger's test were used to evaluate publication bias. Results: A total of 2229 patients from 16 studies were included in this meta-analysis. The results showed that positive YAP expression was closely correlated with GC but not adjacent non-tumor tissue (OR = 8.08, 95% CI = 4.41-14.80). Additionally, YAP overexpression was found to be associated with more advanced TNM stage (OR = 2.68, 95% CI = 1.61-4.48), deeper invasion depth (OR = 2.05, 95% CI = 1.32-3.19), and lymph node metastasis (OR = 1.95, 95% CI = 1.29-2.96). No significant correlation was observed between YAP overexpression and degree of differentiation (OR = 1.17, 95% CI = 0.63-2.16), as well as gender of patients (OR = 1.12, 95% CI = 0.91-1.37) or tumor size (OR = 1.11, 95% CI = 0.82-1.49) of gastric cancer. Conclusions: This meta-analysis demonstrated that YAP might be a promising diagnostic marker and even a therapeutic target for gastric cancer.

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Section: Discussionsupporting

confidence: 78%

Association of Elevated Yes-Associated Protein Expression with Gastric Cancer and Its Clinicopathological Features: A Meta-Analysis

Peng¹,

Yuan²,

Duan³

et al. 2020

JBM

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“…Our previous studies demonstrated that SIRT1 has a protective role in IVDD 31,32 . Furthermore, several studies revealed that SIRT1 plays a key role in mitophagy and apoptosis in a variety of aging-related diseases via SIRT1-Parkin-Mitohphagy pathway [33][34][35][36][37] . In present study, we showed that circERCC2 regulated the expression of SIRT1 by sponging miR-182-5p.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.

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“…This affords F-actin a central position within cellular response networks. Based on previous studies, F-actin dysregulation is associated with gastric cancer migration inhibition via sirtuin 1/mitofusin 2-mediated mitophagy ( 12 , 13 ). Furthermore, F-actin downregulation contributes to rectal cancer mitochondrial apoptosis via activation of the c-Jun N-terminal kinase (JNK)-dynamin-related protein 1-mitochondrial fission-HtrA serine peptidase 2/Omi axis ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F‑actin pathways

et al. 2018

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Mammalian STE20-like kinase 1 (Mst1) is well recognized as a major tumor suppressor in cancer development, growth, metabolic reprogramming, metastasis, cell death and recurrence. However, the roles of Mst1 in non-small cell lung cancer (NSCLC) A549 cell phenotypic alterations remain to be elucidated. The present study aimed to explore the functional role and underlying mechanisms of Mst1 with regards to A549 cell proliferation, migration and apoptosis; this study focused on mitochondrial homeostasis and Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/F-actin pathways. The results demonstrated that Mst1 was downregulated in A549 cells compared with in a normal pulmonary epithelial cell line. Subsequently, overexpression of Mst1 in A549 cells reduced cell viability and promoted cell apoptosis. Furthermore, overexpression of Mst1 suppressed A549 cell proliferation and migration. At the molecular level, the reintroduction of Mst1 in A549 cells led to activation of mitochondrial apoptosis, as evidenced by a reduction in mitochondrial potential, overproduction of ROS, cytochrome c release from the mitochondria into the nucleus, and upregulation of pro-apoptotic protein expression. In addition, Mst1 overexpression was closely associated with impaired mitochondrial respiratory function and suppressed cellular energy metabolism. Functional studies illustrated that Mst1 overexpression activated ROCK1/F-actin pathways, which highly regulate mitochondrial function. Inhibition of ROCK1/F-actin pathways in A549 cells sustained mitochondrial homeostasis, alleviated caspase-9-dependent mitochondrial apoptosis, enhanced cancer cell migration and increased cell proliferation. In conclusion, these data firmly established the regulatory role of Mst1 in NSCLC A549 cell survival via the modulation of ROCK1/F-actin pathways, which may provide opportunities for novel treatment modalities in clinical practice.

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Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

Cited by 67 publications

References 53 publications

Association of Elevated Yes-Associated Protein Expression with Gastric Cancer and Its Clinicopathological Features: A Meta-Analysis

Association of Elevated Yes-Associated Protein Expression with Gastric Cancer and Its Clinicopathological Features: A Meta-Analysis

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

Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F‑actin pathways

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