Hypoxia‐induced SENP3 promotes chemosensitivity and mitochondrial fission via deSUMOylation of Drp1

Abstract

AbstractObjectiveThe study aimed to investigate the effect of the SUMOylation status of Drp1 on mitochondrial fission in CDDP‐treated HNSCC cells cultured under hypoxic conditions.Materials and methodsThe effect of hypoxia on the chemosensitivity of HNCC cells was evaluated by flow cytometry and CCK‐8 assays. The biological function of SUMO‐specific peptidase 3 (SENP3) was evaluated by loss‐of‐function assays both in vitro and in vivo. SENP3‐regulated deSUMOylation of Drp1 were performed with co‐IP assays.ResultsSENP3 expression correlated with chemosensitivity in clinical HNSCC samples subjected to hypoxic conditions. Hypoxia‐induced ROS increased HIF‐1α/SENP3 expression and mitochondrial fission in CDDP‐treated HNSCC cells, and these effects were reversed by NAC treatment. SENP3 knockdown reversed hypoxia‐induced mitochondrial fission and inhibited HNSCC cell apoptosis, which decreased CDDP sensitivity. Furthermore, hypoxia‐induced SENP3 deconjugated SUMO2 from Drp1.ConclusionOur findings revealed that hypoxia‐induced SENP3 facilitates CDDP sensitivity and mitochondrial fission via deSUMOylation of Drp1.