SIRT3-mediated mitochondrial unfolded protein response weakens breast cancer sensitivity to cisplatin

Mitochondrial unfolded protein response plays an important role in the occurrence and development of breast cancer. However, the role of mitochondrial unfolded protein response (UPRmt) in the sensitivity of breast cancer to cisplatin chemotherapy has not yet been cleared.The purpose of this study is to explore the role of mitochondrial unfolded protein response in breast cancer sensitivity to cisplatin.In this study, qRT-PCR, Western blotting, Immunofluorescence, CCK-8, Colony formation, Transwell assay and TUNEL staining assay were used to confirm the role of UPRmt in breast cancer cells treated with cisplatin.Cisplatin increased the levels of UPRmt including CLPP, HSP60, LONP1 in MCF7 and MDA-MB-231 cells. UPRmt inducer Nicotinamide ribose (NR) could promote the proliferation and invasion of breast cancer cells treated with cisplatin. Importantly, SIRT3 was discovered to increase UPRmt in breast cancer cells and silencing of SIRT3 could inhibit the effect of NR in breast cancer.UPRmt regulated by SIRT3 could protect breast cancer cell from cisplatin. Controlling SIRT3-induced UPR may be a potential therapeutic target to increase the sensitivity of breast cancer chemotherapy.