RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization
The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical s...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003152 |
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| author | Siyuan Wu Gaochao Wang Likai Gu Yinjie Zhang Zhihuai Wang |
| author_facet | Siyuan Wu Gaochao Wang Likai Gu Yinjie Zhang Zhihuai Wang |
| author_sort | Siyuan Wu |
| collection | DOAJ |
| description | The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer. |
| format | Article |
| id | doaj-art-0d49ddd27b414fc9a55a04bf878801d0 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-0d49ddd27b414fc9a55a04bf878801d02025-08-20T02:30:34ZengElsevierTranslational Oncology1936-52332025-01-015110218910.1016/j.tranon.2024.102189RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilizationSiyuan Wu0Gaochao Wang1Likai Gu2Yinjie Zhang3Zhihuai Wang4Nanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, ChinaNanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, ChinaNanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, ChinaNanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China; Corresponding author at: Nanjing Medical University, Nanjing, 211166, China.Nanjing Medical University, Nanjing, 211166, China; The Department of Hepato-biliary-pancreatic Surgery, The Institute of Hepatobiliary and Pancreatic Diseases, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China; Corresponding author at: Nanjing Medical University, Nanjing, 211166, China.The study highlights that RPS21, a gene encoding a component of the 40S ribosomal subunit, plays an oncogenic role in hepatocellular carcinoma (HCC) and may influence tumor aggressiveness by affecting antioxidant capacity. RPS21 was found to be upregulated in HCC through RNA-sequencing of clinical samples and analysis of the TCGA database. Kaplan-Meier survival analyses linked higher RPS21 expression to lower survival rates across multiple metrics (OS, PFS, RFS, DSS). Mutation analysis via the cBioPortal showed that primarily amplifications in RPS21 are associated with a poorer prognosis. Tissue microarrays confirmed higher RPS21 levels in tumor samples, which were associated with more advanced clinical stages and grades. Experimental interventions involving lentiviral knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration. These findings were supported by mouse models, which showed impacts on tumor growth and metastasis. Further mechanistic studies indicated that RPS21 modulates the ubiquitination and stability of GPX4, a key player in ferroptosis and oxidative stress regulation in HCC cells. This comprehensive study, which merges bioinformatic analysis with laboratory research, positions RPS21 as a viable target for HCC therapy and opens new pathways for understanding and treating liver cancer.http://www.sciencedirect.com/science/article/pii/S1936523324003152Hepatocellular carcinomaRPS21GPX4ROSFerroptosis |
| spellingShingle | Siyuan Wu Gaochao Wang Likai Gu Yinjie Zhang Zhihuai Wang RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization Translational Oncology Hepatocellular carcinoma RPS21 GPX4 ROS Ferroptosis |
| title | RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization |
| title_full | RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization |
| title_fullStr | RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization |
| title_full_unstemmed | RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization |
| title_short | RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization |
| title_sort | rps21 enhances hepatocellular carcinoma development through gpx4 stabilization |
| topic | Hepatocellular carcinoma RPS21 GPX4 ROS Ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003152 |
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