دورية أكاديمية
The EGR1/miR-139/NRF2 axis orchestrates radiosensitivity of non-small-cell lung cancer via ferroptosis.
| العنوان: | The EGR1/miR-139/NRF2 axis orchestrates radiosensitivity of non-small-cell lung cancer via ferroptosis. |
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| المؤلفون: | Zhang L; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Xu Y; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Cheng Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Zhao J; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China., Wang M; Department of Public Laboratory, Tianjin Medical University Cancer Institute & Hospital, 300060, Tianjin, China., Sun Y; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China., Mi Z; Department of Public Laboratory, Tianjin Medical University Cancer Institute & Hospital, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China. Electronic address: mizeyun@tmu.edu.cn., Yuan Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China. Electronic address: zyuan@tmu.edu.cn., Wu Z; Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China. Electronic address: zwu08@tmu.edu.cn. |
| المصدر: | Cancer letters [Cancer Lett] 2024 Jul 28; Vol. 595, pp. 217000. Date of Electronic Publication: 2024 May 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
| مواضيع طبية MeSH: | MicroRNAs*/genetics , MicroRNAs*/metabolism , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/radiotherapy , Carcinoma, Non-Small-Cell Lung*/pathology , Carcinoma, Non-Small-Cell Lung*/metabolism , Ferroptosis*/genetics , NF-E2-Related Factor 2*/genetics , NF-E2-Related Factor 2*/metabolism , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Lung Neoplasms*/radiotherapy , Lung Neoplasms*/metabolism , Radiation Tolerance*/genetics , Early Growth Response Protein 1*/genetics , Early Growth Response Protein 1*/metabolism , Signal Transduction* , Gene Expression Regulation, Neoplastic*, Humans ; Animals ; Cell Line, Tumor ; Mice ; Male ; Reactive Oxygen Species/metabolism ; A549 Cells ; Mice, Nude ; Female |
| مستخلص: | Radiotherapy is one of the predominant treatment modalities for almost all kinds of malignant cancers, including non-small cell lung cancer (NSCLC). Increasing evidence shows that ionizing radiation (IR) induces reactive oxygen species (ROS) leading to lipid peroxidation and subsequently ferroptosis of cancer cells. However, cancer cells evolve multiple mechanisms against ROS biology resulting in resistance to ferroptosis and radiotherapy, of which NRF2 signaling is one of the most studied. In the current research, we identified that microRNA-139 (miR-139) could be a novel radiosensitizer for NSCLC by inhibiting NRF2 signaling. We found that miR-139 possessed great potential as a diagnostic biomarker for NSCLC and multiple other types of cancer. Overexpression of miR-139 increased radiosensitivity of NSCLC cells in vitro and in vivo. MiR-139 directly targeted cJUN and KPNA2 to impair NRF2 signaling resulting in enhanced IR-induced lipid peroxidation and cellular ferroptosis. We proved KPNA2 to be a binding partner of NRF2 that involved in nuclear translocation of NRF2. Moreover, we found that IR induced miR-139 expression through transcriptional factor EGR1. EGR1 bound to the promoter region and transactivated miR-139. Overall, our findings elucidated the effect of EGR1/miR-139/NRF2 in IR-induced ferroptosis of NSCLC cells and provided theoretical support for the potential diagnostic biomarkers and therapeutic targets for the disease. Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Ferroptosis; NRF2 signaling; Non-small cell lung cancer; ROS; Radiotherapy; microRNA |
| المشرفين على المادة: | 0 (MicroRNAs) 0 (NF-E2-Related Factor 2) 0 (NFE2L2 protein, human) 0 (Early Growth Response Protein 1) 0 (MIRN139 microRNA, human) 0 (EGR1 protein, human) 0 (Reactive Oxygen Species) |
| تواريخ الأحداث: | Date Created: 20240531 Date Completed: 20240614 Latest Revision: 20240621 |
| رمز التحديث: | 20240622 |
| DOI: | 10.1016/j.canlet.2024.217000 |
| PMID: | 38821254 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1872-7980 |
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| DOI: | 10.1016/j.canlet.2024.217000 |