Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China.
Department of Anesthesiology, Second Xiangya Hospital of Central South University, Changsha, China.
Head Neck. 2024 Nov;46(11):2776-2788. doi: 10.1002/hed.27821. Epub 2024 May 21.
The study aimed to investigate the effect of the SUMOylation status of Drp1 on mitochondrial fission in CDDP-treated HNSCC cells cultured under hypoxic conditions.
The 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.
SENP3 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.
Our findings revealed that hypoxia-induced SENP3 facilitates CDDP sensitivity and mitochondrial fission via deSUMOylation of Drp1.
本研究旨在探讨 Drp1 的 SUMOylation 状态对缺氧条件下顺铂处理的头颈部鳞状细胞癌（HNSCC）细胞中线粒体分裂的影响。
通过流式细胞术和 CCK-8 检测评估缺氧对 HNSCC 细胞化疗敏感性的影响。通过体外和体内的功能丧失实验评估 SUMO 特异性肽酶 3（SENP3）的生物学功能。通过共免疫沉淀实验检测 SENP3 调节的 Drp1 的去 SUMOylation。
在接受缺氧处理的临床 HNSCC 样本中，SENP3 的表达与化疗敏感性相关。缺氧诱导的 ROS 增加了 HIF-1α/SENP3 的表达和 CDDP 处理的 HNSCC 细胞中线粒体分裂，NAC 处理可逆转这些效应。SENP3 敲低逆转了缺氧诱导的线粒体分裂并抑制了 HNSCC 细胞凋亡，从而降低了 CDDP 的敏感性。此外，缺氧诱导的 SENP3 将 SUMO2 从 Drp1 上去 SUMOylation。
本研究结果表明，缺氧诱导的 SENP3 通过 Drp1 的去 SUMOylation 促进 CDDP 敏感性和线粒体分裂。
