Background and objective: Transcriptional coactivator with PDZ-binding motif (TAZ) has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of TAZ and mitochondrial homeostasis in liver cancer viability have not been explored. The aim of our study was to investigate the influence of TAZ on HepG2 liver cancer cell apoptosis.
Materials and methods: HepG2 liver cancer cell was used in the present study, and shRNA against TAZ was transfected into HepG2 cell to knockdown TAZ expression. Mitochondrial function was analyzed using Western blotting, immunofluorescence assay, and flow cytometry. Pathway blocker was used to confirm the role of CaMKII pathway in TAZ-mediated cancer cell death.
Results: Our results indicated that TAZ deletion induced death in HepG2 cell via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, were activated by TAZ deletion. Furthermore, we found that TAZ affected mitochondrial stress by triggering mitochondrial elongation factor 1 (MIEF1)-related mitochondrial dysfunction. The loss of MIEF1 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that TAZ regulated MIEF1 expression via the CaMKII signaling pathway. Blockade of the CaMKII pathway prevented TAZ-mediated MIEF1 upregulation and improved cancer cell survival.
Conclusion: Taken together, our results highlight the key role of TAZ as a master regulator of HepG2 liver cancer cell viability via the modulation of MIEF1-related mitochondrial stress and the CaMKII signaling pathway. These findings define TAZ and MIEF1-related mitochondrial dysfunction as tumor suppressors that act by promoting cancer apoptosis via the CaMKII signaling pathway, with potential implications for new approaches to liver cancer therapy.
Keywords: TAZ, liver cancer, death, MIEF1, CaMKII signaling pathway