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

Autor: Mao Y; 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., Liu K; Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China., Yang Y; Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China., Liang Y; Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai, China., Gong Z; Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China., Wu K; Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, China.
Jazyk: angličtina
Zdroj: Head & neck [Head Neck] 2024 Nov; Vol. 46 (11), pp. 2776-2788. Date of Electronic Publication: 2024 May 21.
DOI: 10.1002/hed.27821
Abstrakt: Objective: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: Our findings revealed that hypoxia-induced SENP3 facilitates CDDP sensitivity and mitochondrial fission via deSUMOylation of Drp1.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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