Suppression of Tafazzin promotes thyroid cancer apoptosis via activating the JNK signaling pathway and enhancing INF2‐mediated mitochondrial fission

Li, Xiaobin; Wu, Mei; An, Duo; Hu, Yuan; Li, Zengze; Song, Yimin; Liu, Ziwen

doi:10.1002/jcp.28287

Cited by 17 publications

(15 citation statements)

References 68 publications

(89 reference statements)

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“…Similar results were also noted in liver cancer in response to cytokine-based therapy [29, 30]. This finding is also validated in thyroid cancer that activation of JNK pathway enhances mitochondrial fission and promotes cancer cell death [31, 32]. Based on the above information, we wanted to know whether JNK pathway was involved in mitochondrial fission in Mst1/Yap-modified cell viability in MDA-T32 cell in vitro.…”

Section: Introductionsupporting

confidence: 60%

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

Zhang

Cui

et al. 2019

Cancer Cell Int

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Background Cancer cell viability is strongly modulated by the Hippo pathway, which includes mammalian STE20-like protein kinase 1 (Mst1) and yes-associated protein (Yap). Although the roles of Mst1 and Yap in thyroid carcinoma cell death have been fully addressed, no study has determined whether differential modification of Mst1 and Yap could further suppress thyroid carcinoma progression. The aim of our study was to explore the antiapoptotic effects exerted by combined Mst1 overexpression and Yap knockdown in thyroid carcinoma MDA-T32 cells in vitro. Methods Mst1 adenovirus and Yap shRNA were transfected into MDA-T32 cells to overexpress Mst1 and inhibit Yap, respectively. Cell viability and death were determined via an MTT assay, a TUNEL assay and western blotting. Mitochondrial function, mitochondrial fission and pathway studies were performed via western blotting and immunofluorescence. Results The results of our study showed that combined Mst1 overexpression and Yap knockdown further augmented MDA-T32 cell death by mediating mitochondrial damage. In addition, cancer cell migration and proliferation were suppressed by combined Mst1 overexpression and Yap knockdown. At the molecular level, mitochondrial membrane potential, ATP production, respiratory function, and caspase-9-related apoptosis were activated by combined Mst1 overexpression and Yap knockdown. Further, we found that fatal mitochondrial fission was augmented by combined Mst1 overexpression and Yap knockdown in a manner dependent on the JNK-MIEF1 pathway. Inhibition of JNK-MIEF1 pathway activity abolished the proapoptotic effects exerted by Mst1/Yap on MDA-T32 cells. Conclusions Taken together, our data suggest that Mst1 activation and Yap inhibition coordinate to augment thyroid cancer cell death by controlling the JNK-MIEF1-mitochondria pathway, suggesting that differential regulation of the core Hippo pathway components is potentially a novel therapeutic tool for the treatment of thyroid cancer. Electronic supplementary material The online version of this article (10.1186/s12935-019-0860-8) contains supplementary material, which is available to authorized users.

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Section: Introductionsupporting

confidence: 60%

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

Zhang

Cui

et al. 2019

Cancer Cell Int

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“…Numerous experiments have been conducted to verify the beneficial effects of melatonin on fatty liver disease (Galano & Reiter, ), liver cancer (Lee, Hwang, Reiter, & Back, ), hyperglycemia‐related hepatic dysfunction (Lochner, Marais, & Huisamen, ), and alcohol‐induced liver damage (Zhou, Wang, Zhu, Hu, & Ren, ). But the hepatic protection mechanisms exerted by melatonin in inflammation‐attached hepatocyte remain to be elucidated (X. Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Melatonin attenuates TNF‐α‐mediated hepatocytes damage via inhibiting mitochondrial stress and activating the Akt‐Sirt3 signaling pathway

Liu

Zhao

et al. 2019

Journal Cellular Physiology

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The role of mitochondrial dysfunction and its molecular mechanism in inflammationinduced acute liver failure (ALF) remain unknown. Despite the numerous studies performed to date, very few therapies are available for inflammation-induced ALF.Therefore, our study is aimed to explore the regulatory effects of mitochondrial stress and the Akt-Sirt3 pathway on the development of TNF-α-induced hepatocyte death and assess the therapeutic effects of melatonin on the damaged liver. Our results exhibited that TNF-α treatment induced hepatocyte damage in vitro; the effect of which was dose-dependently inhibited by melatonin. At the molecular level, TNF-α-treated hepatocytes expressed lower levels of Sirt3 and subsequently exhibited mitochondrial stress. Interestingly, melatonin treatment improved mitochondrial bioenergetics, reduced mitochondrial oxidative stress, reversed mitochondrial dynamics, and repressed mitochondrial apoptosis by reversing the decrease in Sirt3 expression after TNF-α challenge. In addition, we found that melatoninregulated Sirt3 expression in a manner dependent on the Akt pathway. Blockade of the Akt pathway abolished the protective exerted by melatonin on mitochondria and hepatocyte under TNF-α treatment. In conclusion, TNF-α promotes hepatocyte apoptosis by inducing mitochondrial stress. However, melatonin significantly increases the activity of the Akt/Sirt3 axis and consequently maintains mitochondrial homeostasis, restoring hepatocyte viability in an inflammatory environment. Thus, the information compiled here might provide important perspectives for the use of melatonin in the clinic for preventive and therapeutic applications in patients with ALF based on its anti-inflammatory and mitochondria-protective effects. K E Y W O R D Sacute liver failure, Akt pathway, hepatocyte death, melatonin, mitochondria, Sirt3

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“…MYO9A, encodes an unconventional myosin, which is required for collective migration of epithelial cells and thus serves as a potent promoter in progression and metastasis of cancers of epithelial origin (Friedl and Gilmour, 2009;Ouderkirk and Krendel, 2014). TAZ encodes tafazzin whose overexpression promotes tumorigenicity in many cancers and its inhibition also induces tumor cell apoptosis (Chen et al, 2017a;Li et al, 2019a;Pathak et al, 2014). GADD45GIP1, also known as CRIF1, encodes a nuclear-localized protein that may be induced by TP53 and regulates cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Classification of clear cell renal cell carcinoma based on PKM alternative splicing

Turanlı

Juszczak

et al. 2020

Heliyon

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Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.

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Suppression of Tafazzin promotes thyroid cancer apoptosis via activating the JNK signaling pathway and enhancing INF2‐mediated mitochondrial fission

Cited by 17 publications

References 68 publications

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

RETRACTED: Melatonin attenuates TNF‐α‐mediated hepatocytes damage via inhibiting mitochondrial stress and activating the Akt‐Sirt3 signaling pathway

Classification of clear cell renal cell carcinoma based on PKM alternative splicing

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