PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway
Abstract Oral cavity squamous cell carcinoma (OSCC) represents the most prevalent malignancy among head and neck squamous cell carcinomas (HNSCCs). Standard treatment modalities include surgical resection combined with radiation and chemotherapy. However, locoregional failure remains a critical issu...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02286-2 |
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| author | Chun-I Wang Cheng-Yi Chen Ting-Wen Chen Chun-Chia Cheng Shu-Wen Hong Tsung-You Tsai Kai-Ping Chang |
| author_facet | Chun-I Wang Cheng-Yi Chen Ting-Wen Chen Chun-Chia Cheng Shu-Wen Hong Tsung-You Tsai Kai-Ping Chang |
| author_sort | Chun-I Wang |
| collection | DOAJ |
| description | Abstract Oral cavity squamous cell carcinoma (OSCC) represents the most prevalent malignancy among head and neck squamous cell carcinomas (HNSCCs). Standard treatment modalities include surgical resection combined with radiation and chemotherapy. However, locoregional failure remains a critical issue affecting the prognosis of OSCC patients, largely due to tumor resistance against radiation or chemotherapy. In this study, we established a gene database related to OSCC recurrence and identified PSMA2 as a novel molecule influencing prognosis in OSCC patients. An independent Taiwanese cohort confirmed that elevated PSMA2 transcript levels were associated with poorer prognosis and contributed to the chemo- and radioresistance phenotype in OSCC. Furthermore, we confirmed that PSMA2 regulates cell cycle, mitochondrial dysfunction, and mitophagy, thereby contributing to carcinogenesis and resistance. Notably, mitophagy inducer exhibit antitumor effects in PSMA2-overexpressing OSCC xenograft mouse model. Collectively, our results provide a mechanistic understanding of the atypical function of PSMA2 in promoting OSCC recurrence. |
| format | Article |
| id | doaj-art-d07c682a14024963bd84c64a017cd802 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-d07c682a14024963bd84c64a017cd8022025-01-12T12:08:17ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111210.1038/s41420-025-02286-2PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathwayChun-I Wang0Cheng-Yi Chen1Ting-Wen Chen2Chun-Chia Cheng3Shu-Wen Hong4Tsung-You Tsai5Kai-Ping Chang6Department of Biochemistry, School of Medicine, China Medical UniversityDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung UniversityInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung UniversityRadiation Biology Research Center, Institute for Radiological Research, Chang Gung University/ Linkou Chang Gung Memorial HospitalDepartment of Biochemistry, School of Medicine, China Medical UniversityDepartment of Otolaryngology-Head & Neck Surgery, Linkou Chang Gung Memorial HospitalDepartment of Otolaryngology-Head & Neck Surgery, Linkou Chang Gung Memorial HospitalAbstract Oral cavity squamous cell carcinoma (OSCC) represents the most prevalent malignancy among head and neck squamous cell carcinomas (HNSCCs). Standard treatment modalities include surgical resection combined with radiation and chemotherapy. However, locoregional failure remains a critical issue affecting the prognosis of OSCC patients, largely due to tumor resistance against radiation or chemotherapy. In this study, we established a gene database related to OSCC recurrence and identified PSMA2 as a novel molecule influencing prognosis in OSCC patients. An independent Taiwanese cohort confirmed that elevated PSMA2 transcript levels were associated with poorer prognosis and contributed to the chemo- and radioresistance phenotype in OSCC. Furthermore, we confirmed that PSMA2 regulates cell cycle, mitochondrial dysfunction, and mitophagy, thereby contributing to carcinogenesis and resistance. Notably, mitophagy inducer exhibit antitumor effects in PSMA2-overexpressing OSCC xenograft mouse model. Collectively, our results provide a mechanistic understanding of the atypical function of PSMA2 in promoting OSCC recurrence.https://doi.org/10.1038/s41420-025-02286-2 |
| spellingShingle | Chun-I Wang Cheng-Yi Chen Ting-Wen Chen Chun-Chia Cheng Shu-Wen Hong Tsung-You Tsai Kai-Ping Chang PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway Cell Death Discovery |
| title | PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| title_full | PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| title_fullStr | PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| title_full_unstemmed | PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| title_short | PSMA2 promotes chemo- and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| title_sort | psma2 promotes chemo and radioresistance of oral squamous cell carcinoma by modulating mitophagy pathway |
| url | https://doi.org/10.1038/s41420-025-02286-2 |
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