Yap-Hippo promotes A549 lung cancer cell death via modulating MIEF1-related mitochondrial stress and activating JNK pathway

Zhou, Jiayu; Zhang, Shizhen; Li, Zhijun; Chen, Zhoumiao; Xu, Yong; Ye, Weiwen; He, Zhengfu

doi:10.1016/j.biopha.2019.108754

Cited by 8 publications

(3 citation statements)

References 60 publications

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“…Increased MIEF1 expression impairs mitochondrial dynamics, leading to mitochondrial fragmentation, which has been acknowledged as an early event in mitochondrial apoptosis initiation. For example, in lung cancer, MIEF1-dependent activation of mitochondria promotes mitochondrial stress and augments mitochondrial apoptosis in A549 lung cancer cells [25]. In addition, reperfusion-mediated cardiomyocyte death and endothelial damage are also tightly controlled by MIEF1 in a manner dependent on mitochondrial fission [26].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK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

confidence: 99%

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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“…However, DIS3 and PAPD5 may act as RNA ectodomain complexes involved in the degradation or transcription of various cellular RNAs ( Hu et al, 2020 ; Liu et al, 2020 ). Moreover, MIEF1 and LY6E may mediate different signalling pathways to induce apoptosis in the corresponding cancer cells ( Yeom et al, 2016 ; Hou et al, 2019 ; Zhou et al, 2019 ). The expression level of TRIM58 protein may be related to the prognosis of patients with LUAD and COAD ( Liu et al, 2018 ; Chen et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy

2022

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Background:FAM46C is a common mutated gene in tumours. A comprehensive understanding of the relationship between FAM46C expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets.Methods: Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the FAM46C protein levels in normal and cancerous tissues. The genetic variation of FAM46C was characterised using cBioPortal. The clinical prognostic value of FAM46C and the impact of FAM46C expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan–Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with FAM46C. Correlations between FAM46C expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between FAM46C expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between FAM46C expression and immune activation, suppression genes and immune chemokines.Results: The expression level of FAM46C was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. FAM46C was positively correlated with the abundance of CD4+ T cells, CD8+ T cells and plasma B lymphocytes in the tumour microenvironment. FAM46C exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high FAM46C expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer.Conclusion: Our study suggests that FAM46C can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.

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“…Similar to lung cancer, Gobbi et al [ 55 ] demonstrated that LATS2, TAOK1, and NF2 act as Hippo pathway genes and are the primary determinants of the sensitivity of lung cancer cells to JQ1 pan-BETi. YAP-Hippo regulates MIEF1-related mitochondrial stress and activates the JNK pathway to promote the death of A549 lung cancer cells [ 56 ]. As a human retrovirus, HTLV-1 results in HTLV-1-related myelopathy/tropical spastic paraparesis and other inflammatory illnesses; HTLV-1 test is not a routine test, while approximately 5% of patients were found to be carriers of HTLV-1 in areas where HTLV-1 is endemic [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA signature for predicting the prognostic biomarker of squamous cell lung carcinoma

Liu

Dong

et al. 2022

PLoS ONE

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As explorations deepen, the role of microRNAs (miRNAs) in lung squamous cell carcinoma (LUSC), from its emergence to metastasis and prognosis, has elicited extensive concern. LUSC-related miRNA and mRNA samples were acquired from The Cancer Genome Atlas (TCGA) database. The data were initially screened and pretreated, and the R platform and series analytical tools were used to identify the specific and sensitive biomarkers. Seven miRNAs and 15 hub genes were found to be closely related to the overall survival of patients with LUSC. Determination of the expression of these miRNAs can help improve the overall survival of LUSC patients. The 15 hub genes correlated with overall survival (OS). The new miRNA markers were identified to predict the prognosis of LUSC. The findings of this study offer novel views on the evolution of precise cancer treatment approaches with high reliability.

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Yap-Hippo promotes A549 lung cancer cell death via modulating MIEF1-related mitochondrial stress and activating JNK pathway

Cited by 8 publications

References 60 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

FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy

Identification of miRNA signature for predicting the prognostic biomarker of squamous cell lung carcinoma

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