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The m6A modification of ACSL4 mRNA sensitized esophageal squamous cell carcinoma to irradiation via accelerating ferroptosis.
Jin, Yingying; Pan, Shupei; Wang, Mincong; Huang, Shan; Ke, Yue; Li, Dan; Luo, Hen; Kou, Zhanfeng; Shi, Dongwen; Kou, Weihua; Fu, Hongxiao; Pan, Jiyuan.
Afiliación
  • Jin Y; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Pan S; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Wang M; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Huang S; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Ke Y; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Li D; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Luo H; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Kou Z; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Shi D; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Kou W; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Fu H; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Pan J; Department of Radiation Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Cell Biol Int ; 2024 Sep 16.
Article en En | MEDLINE | ID: mdl-39285560
ABSTRACT
Radioresistance is a major obstacle for the therapy of esophageal squamous cell carcinoma (ESCC) and lead to a poor prognosis. Ferroptosis is supposed to be responsible for radioresistance. However, the ferroptosis-induced radioresistance in ESCC and its related regulatory mechanisms are not yet fully understood. In this study, human ESCC cell line and the corresponding radioresistance cells were irradiated with 6 megavolts (MV) X-ray. It was showed that irradiation led to less ferroptosis in radioresistant ESCC cells as compared to the parental cells, as depicted by transmission electron microscopy, intracellular Fe2+ iron contents, lipid peroxidation, and expression of COX2. The increase of ASCL4 expression levels in radioresistant cells after radiotherapy was smaller than that in the parental cells. ACSL4 overexpression significantly enhanced ferroptosis. The fold increase in ACSL4 m6A modification in the radioresistant cells was significantly smaller than that in the parental cells as detected by methylated RNA immunoprecipitation with qRT-PCR. METTL14 overexpression accelerated ferroptosis induced by irradiation via upregulating m6A modification of ACSL4 mRNA. In conclusions, ferroptosis ablation was responsible for the radioresistant of ESCC. The METTL14-mediated m6A modification of ACSL4 mRNA sensitized ESCC to irradiation via accelerating ferroptosis. This study sheds new light on our understanding of radioresistant in ESCC, and provides potential strategies for ESCC radiotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biol Int Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biol Int Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido