RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK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

Abstract

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.

Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis

“…Mitochondria function as a cellular powerhouse to provide a constant supply of ATP for performing numerous biological processes such as metabolism, proliferation, growth, metastasis, differentiation, angiogenesis, and apoptosis [ 1 ]. Their involvement in the development and progression of thyroid carcinoma is evident from the fact that mitochondrial proteins serve as potential targets of chemotherapeutic receptor tyrosine kinase inhibitor drugs such as vandetanib and cabozantinib [ 2 , 3 ]. Moreover, the inhibition of mitochondrial function via disruption of oxidative phosphorylation has been shown to enhance the response to chemotherapy [ 4 ].…”

FOXG1 improves mitochondrial function and promotes the progression of nasopharyngeal carcinoma

“…Mitochondrial dysfunction is reported to be associated with cancer cell death ( 19 ). To investigate whether FOXG1 was involved in the regulation of NPC mitochondrial function, the copy number of mtDNA was detected via RT-qPCR.…”

“…Changes in the structure and function of mitochondria in tumor cells lead to an increase in the absorption and utilization of glutamine, thereby meeting the bioenergy requirements of tumor cells, which is known as tumor mitochondrial metabolic reprogramming ( 17 ). Accumulating evidence has revealed that mitochondria serve an important role in cancer metabolism, proliferation, apoptosis and metastasis ( 18 , 19 ). However, the specific regulatory relationship between FOXG1 and NPC progression remains unknown.…”

Sirtuin 3 attenuates neuroinflammation-induced apoptosis in BV-2 microglia

“…At the molecular level, Sirt3 inactivated the Mst1-JNK pathway and thus suppressed the expression of SRV2, a novel mediator of mitochondrial fission. The Mst1-JNK axis is known to control mitochondrial fission in liver cancer [43], hyperglycemia-induced vascular dysfunction [44], thyroid carcinoma [45], breast cancer [46], acute cardiac stress [47], and colorectal cancer [48]. In addition, SRV2 induces mitochondrial fission by promoting F-actin polymerization [49, 50].…”