mir-373 suppresses cell proliferation and apoptosis via regulation of sirt1/pgc-1α/nrf2 axis in pancreatic cancer

Objective: our study aimed to investigate function and mechanism of mir-373 in proliferation and apoptosis of pancreatic cancer (pc) cells by regulating nad+-dependent histone deacetylase sirtulin 1 (sirt1). materials and methods: this experimental study included two pc cell lines aspc-1 and panc-1 in which expression levels of mir-373 and sirt1 were manipulated. the level of mir-373 was detected by reverse transcription quantitative polymerase chain reaction (rt-qpcr) method. expression levels of sirt1, bcl-2, bax, cleaved caspase-8/9/3, parp, pgc-1α, nrf2, enos and inos were examined via rt-qpcr and western blotting, respectively. the binding sites of mir-373 on the sirt1 were examined via dual-luciferase assay. cell proliferation and apoptosis were examined by mtt assay, colony formation assay, annexin-v/pi staining and tunel assay. the oxidative metabolic changes were monitored by reactive oxygen species (ros), malondialdehyde (mda) and superoxide dismutase (sod) detection. results: mir-373 could specifically target the 3’-utr of sirt1 and reduce its expression in pc cells. either elevated expression of mir-373 or partial loss of sirt1 inhibited cell proliferation and induced cell apoptosis. accumulation of bax and cleaved caspase-8/9/3, inhibition of pgc-1α/nrf2 pathway, increase oxidative stress and reduction of bcl-2 as well as uncleaved parp were found in the presence of mir-373 or the absence of sirt1. overexpression of sirt1 could reduce anti-proliferative and pro-apoptotic effects of mir-373. conclusion: overall, this study concluded that mir-373-dependent sirt1 inhibition displays anti-proliferative and proapoptotic roles in pc cells via pgc-1α/nrf2 pathway, which highlights mir-373 as a potential target for pc treatment.