RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization
Siyuan Wu1, Gaochao Wang1, Likai Gu1
1Nanjing 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.
Translational Oncology
|November 15, 2024
Summary
The gene RPS21 promotes liver cancer (hepatocellular carcinoma) by increasing tumor aggressiveness and affecting cell growth. Targeting RPS21 offers a potential new therapy for liver cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with limited effective therapies.
- Understanding the molecular drivers of HCC progression is crucial for developing targeted treatments.
- The role of ribosomal protein S21 (RPS21) in HCC pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the oncogenic role of RPS21 in hepatocellular carcinoma.
- To explore the correlation between RPS21 expression and HCC patient prognosis.
- To elucidate the underlying mechanisms by which RPS21 influences HCC progression and oxidative stress.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database and clinical samples.
- Kaplan-Meier survival analysis and mutation analysis using cBioPortal.
- Experimental validation using cell culture (lentiviral knockdown/overexpression) and mouse models.
- Mechanistic studies involving ubiquitination and stability assays of GPX4.
Main Results:
- RPS21 is significantly upregulated in HCC tissues and associated with advanced clinical stages and poorer patient survival (OS, PFS, RFS, DSS).
- RPS21 amplification is linked to unfavorable prognosis in HCC.
- RPS21 knockdown inhibits HCC cell proliferation and migration, while overexpression enhances these processes.
- RPS21 modulates GPX4 stability, impacting ferroptosis and oxidative stress in HCC cells.
Conclusions:
- RPS21 functions as an oncogene in hepatocellular carcinoma.
- RPS21 expression levels and genetic alterations are significant prognostic markers for HCC.
- Targeting RPS21 presents a promising therapeutic strategy for hepatocellular carcinoma.
- RPS21's role in regulating oxidative stress and ferroptosis provides new insights into HCC treatment.
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