Inhibition of TRF1 can accelerate aging and induce autophagy through the P53-SIRT6 pathway in glioblastoma multiforme

Abstract

Abstract Objective To study the effect of TRF1 on the growth and proliferation of GBM and the specific underlying molecular mechanism. Methods First, we investigated whether TRF1 is an oncogene in GBM by bioinformatics. Next, we knocked down TRF1 in GBM cells, treated the cells with NMN (which activates SIRT6), and then investigated the growth and proliferation of the cells. And we measured the level of telomere DNA damage in these cells. Then, the biological relationship among TRF1, P53, and SIRT6 was determined by STRING database analysis, Western blotting and qRT-PCR. Finally, we examined the levels of cellular senescence and autophagy. Results TRF1 is an important oncogene in GBM. TRF1 knockdown significantly inhibited the growth and proliferation of GBM cells. SIRT6 contributed to reversing the TRF1 knockdown-mediated decrease in GBM cell viability. Knocking down TRF1 caused telomere damage in GBM cells, while SIRT6 attenuated this telomere damage. In GBM cells, inhibition of TRF1 decreased SIRT6 expression through the P53 pathway. In addition, knockdown of TRF1 lead to senescence and induced autophagy in GBM cells, while SIRT6 inhibited cellular aging and autophagy. Conclusion Knocking down TRF1 can accelerate aging and autophagy in GBM through P53-SIRT6 pathway.