EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma
Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with poorly understood underlying molecular mechanisms. Ferroptosis, a form of programmed cell death, is not fully elucidated in NPC. Method: We conducted quantitative proteomics to detect dysregulated proteins in NPC tissues. Th...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003772 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591868425142272 |
|---|---|
| author | Xianghui Chen Xiaoyan Wang Yuxia Zou Yan Wang Tingting Duan Zijie Zhou Yi Huang Qing Ye |
| author_facet | Xianghui Chen Xiaoyan Wang Yuxia Zou Yan Wang Tingting Duan Zijie Zhou Yi Huang Qing Ye |
| author_sort | Xianghui Chen |
| collection | DOAJ |
| description | Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with poorly understood underlying molecular mechanisms. Ferroptosis, a form of programmed cell death, is not fully elucidated in NPC. Method: We conducted quantitative proteomics to detect dysregulated proteins in NPC tissues. The levels of endoplasmic reticulum membrane protein complex 2 (EMC2) in NPC tissue microarrays were evaluated by immunohistochemistry, and the prognostic value of EMC2 was analyzed in NPC patients. The role of EMC2 in ferroptosis and carcinogenesis was determined through in vitro and in vivo experiments. Quantitative proteomics, protease inhibition, ubiquitin detection, and rescue experiments were performed to explore the mechanism of EMC2-regulated ferroptosis. Results: Significantly upregulated EMC2 was detected in NPC, and it was closely related to the characteristics of tumor progression. Elevated EMC2 was obviously correlated with poor survival in patients with NPC. EMC2 knockdown promoted ferroptosis, inhibiting cell viability, migration, and invasion, and enhancing the efficacy of cisplatin in NPC cells. Conversely, EMC2 overexpression contributed to ferroptosis repression, malignant progression, and reduced the efficacy of cisplatin. In addition, EMC2 knockdown suppressed xenograft tumor growth and enhanced ferroptosis in nude mice. Mechanistically, we identified transferrin receptor (TFRC) as a critical downstream protein. EMC2 interacted with TFRC and promoted its ubiquitin-proteasomal degradation. EMC2 regulated ferroptosis by mediating the level of TFRC. Conclusions: EMC2 suppresses ferroptosis and promotes tumor progression, and the EMC2-TFRC axis is a novel ferroptosis regulatory pathway. EMC2 is a potentially biomarker and therapeutic target for NPC. |
| format | Article |
| id | doaj-art-c1c4b10592134bf491033cbfa223be0d |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-c1c4b10592134bf491033cbfa223be0d2025-01-22T05:41:28ZengElsevierTranslational Oncology1936-52332025-02-0152102251EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinomaXianghui Chen0Xiaoyan Wang1Yuxia Zou2Yan Wang3Tingting Duan4Zijie Zhou5Yi Huang6Qing Ye7Shengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, China; Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, China; Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 571199, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, ChinaDepartment of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 571199, ChinaCollege of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaShengli Clinical Medical College of Fujian Medical University, Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, China; Corresponding author.Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with poorly understood underlying molecular mechanisms. Ferroptosis, a form of programmed cell death, is not fully elucidated in NPC. Method: We conducted quantitative proteomics to detect dysregulated proteins in NPC tissues. The levels of endoplasmic reticulum membrane protein complex 2 (EMC2) in NPC tissue microarrays were evaluated by immunohistochemistry, and the prognostic value of EMC2 was analyzed in NPC patients. The role of EMC2 in ferroptosis and carcinogenesis was determined through in vitro and in vivo experiments. Quantitative proteomics, protease inhibition, ubiquitin detection, and rescue experiments were performed to explore the mechanism of EMC2-regulated ferroptosis. Results: Significantly upregulated EMC2 was detected in NPC, and it was closely related to the characteristics of tumor progression. Elevated EMC2 was obviously correlated with poor survival in patients with NPC. EMC2 knockdown promoted ferroptosis, inhibiting cell viability, migration, and invasion, and enhancing the efficacy of cisplatin in NPC cells. Conversely, EMC2 overexpression contributed to ferroptosis repression, malignant progression, and reduced the efficacy of cisplatin. In addition, EMC2 knockdown suppressed xenograft tumor growth and enhanced ferroptosis in nude mice. Mechanistically, we identified transferrin receptor (TFRC) as a critical downstream protein. EMC2 interacted with TFRC and promoted its ubiquitin-proteasomal degradation. EMC2 regulated ferroptosis by mediating the level of TFRC. Conclusions: EMC2 suppresses ferroptosis and promotes tumor progression, and the EMC2-TFRC axis is a novel ferroptosis regulatory pathway. EMC2 is a potentially biomarker and therapeutic target for NPC.http://www.sciencedirect.com/science/article/pii/S1936523324003772EMC2FerroptosisNasopharyngeal carcinomaTFRC |
| spellingShingle | Xianghui Chen Xiaoyan Wang Yuxia Zou Yan Wang Tingting Duan Zijie Zhou Yi Huang Qing Ye EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma Translational Oncology EMC2 Ferroptosis Nasopharyngeal carcinoma TFRC |
| title | EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma |
| title_full | EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma |
| title_fullStr | EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma |
| title_full_unstemmed | EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma |
| title_short | EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma |
| title_sort | emc2 suppresses ferroptosis via regulating tfrc in nasopharyngeal carcinoma |
| topic | EMC2 Ferroptosis Nasopharyngeal carcinoma TFRC |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003772 |
| work_keys_str_mv | AT xianghuichen emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT xiaoyanwang emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT yuxiazou emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT yanwang emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT tingtingduan emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT zijiezhou emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT yihuang emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma AT qingye emc2suppressesferroptosisviaregulatingtfrcinnasopharyngealcarcinoma |