Depletion of C3orf1/TIMMDC1 Inhibits Migration and Proliferation in 95D Lung Carcinoma Cells
AbstractIn our previous study, we identified an association of high expression of c3orf1, also known as TIMMDC1 (translocase of inner mitochondrial membrane domain-containing protein 1), with metastatic characteristics in lung carcinoma cells. To investigate the preliminary function and mechanism of this mitochondrial protein, we depleted C3orf1 expression by introducing siRNA into 95D lung carcinoma cells. We demonstrated that C3orf1 depletion significantly suppressed 95D cell growth and migration. We confirmed C3orf1 localization in the inner mitochondrial membrane and showed that mitochondrial viability, membrane potential, and ATPase activity were remarkably reduced upon depletion of C3orf1. Microarray data indicated that genes involved in regulation of cell death, migration, and cell-cycle arrest were significantly altered after C3orf1 depletion for 48 h. The expression of genes involved in focal adhesion, ECM-receptor interaction, and p53-signaling pathways were notably altered. Furthermore, cell-cycle arrest genes such as CCNG2 and PTEN as well as genes involved in cell migration inhibition, such as TIMP3 and COL3A1, were upregulated after C3orf1 depletion in 95D cells. Concurrently, expression of the migration-promoting gene NUPR1 was markedly reduced, as confirmed by real-time PCR. We conclude that C3orf1 is critical for mitochondrial function, migration, and proliferation in 95D lung carcinoma cells. Depletion of C3orf1 inhibited cell migration and cell proliferation in association with upregulation of genes involved in cell-cycle arrest and cell migration inhibition. These results suggest that C3orf1 (TIMMDC1) may be a viable treatment target for lung carcinoma, and that further study of the role of this protein in lung carcinoma pathogenesis is justified. View Full-Text
Share & Cite This Article
Wu, H.; Wang, W.; Xu, H. Depletion of C3orf1/TIMMDC1 Inhibits Migration and Proliferation in 95D Lung Carcinoma Cells. Int. J. Mol. Sci. 2014, 15, 20555-20571.
Wu H, Wang W, Xu H. Depletion of C3orf1/TIMMDC1 Inhibits Migration and Proliferation in 95D Lung Carcinoma Cells. International Journal of Molecular Sciences. 2014; 15(11):20555-20571.Chicago/Turabian Style
Wu, Huiling; Wang, Wenbing; Xu, Huaxi. 2014. "Depletion of C3orf1/TIMMDC1 Inhibits Migration and Proliferation in 95D Lung Carcinoma Cells." Int. J. Mol. Sci. 15, no. 11: 20555-20571.