Stabilization of hypoxia-inducible factor 1 alpha(HIF1α),which plays a pivotal role in regulating cellular responses to insufficient oxygen,is implicated in cancer progression,particularly epithelial-mesenchymal tran...Stabilization of hypoxia-inducible factor 1 alpha(HIF1α),which plays a pivotal role in regulating cellular responses to insufficient oxygen,is implicated in cancer progression,particularly epithelial-mesenchymal transition and metastatic dissemination.Despite its crucial role in tumorigenesis,the precise mechanisms governing HIF1αstabilization under varying tumor microenvironmental conditions are not fully understood.In this study,we show that stabilization of HIF1αin metastasizing melanoma under mild hypoxia is regulated primarily by mitochondrial reactive oxygen species(ROS)rather than by reduced oxygen levels.Activated HIF1αsuppresses the expression of cyclophilin D(CypD),a regulator of the mitochondrial permeability transition pore(mPTP),as a reciprocal regulatory mechanism to sustain HIF1 signaling via upregulation of microRNAs miR-23a and miR-27a.展开更多
基金supported by a National Research Foundation of Korea(NRF)grantfunded by the Korean government(MSIT)(NRF-2022R1C1C2010351,2022M3E5F2017408,RS-2024-00342382).
文摘Stabilization of hypoxia-inducible factor 1 alpha(HIF1α),which plays a pivotal role in regulating cellular responses to insufficient oxygen,is implicated in cancer progression,particularly epithelial-mesenchymal transition and metastatic dissemination.Despite its crucial role in tumorigenesis,the precise mechanisms governing HIF1αstabilization under varying tumor microenvironmental conditions are not fully understood.In this study,we show that stabilization of HIF1αin metastasizing melanoma under mild hypoxia is regulated primarily by mitochondrial reactive oxygen species(ROS)rather than by reduced oxygen levels.Activated HIF1αsuppresses the expression of cyclophilin D(CypD),a regulator of the mitochondrial permeability transition pore(mPTP),as a reciprocal regulatory mechanism to sustain HIF1 signaling via upregulation of microRNAs miR-23a and miR-27a.
