RPL28 mediates sorafenib resistance in hepatocellular carcinoma by downregulating CDC6 expression.
Yi Shi1, Fangfang Chen1, Yuanyuan Weng1
1Department of Molecular Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
Frontiers in Oncology
|March 4, 2026
Summary
Ribosomal protein L28 (RPL28) drives sorafenib resistance in hepatocellular carcinoma (HCC) by upregulating CDC6. Targeting the RPL28-CDC6 pathway may overcome drug resistance in advanced HCC.
Area of Science:
- Oncology
- Molecular Biology
- Drug Resistance Mechanisms
Background:
- Sorafenib is a key targeted therapy for advanced hepatocellular carcinoma (HCC).
- Resistance to sorafenib significantly limits its clinical effectiveness in HCC patients.
- The precise molecular mechanisms of sorafenib resistance in HCC are not fully understood, with the role of ribosomal proteins (RPs) being an area of ongoing investigation.
Purpose of the Study:
- To investigate the functional role of ribosomal protein L28 (RPL28) in sorafenib resistance in HCC.
- To elucidate the molecular mechanisms by which RPL28 influences sorafenib sensitivity and resistance in HCC.
- To identify potential therapeutic targets for overcoming sorafenib resistance in HCC.
Main Methods:
- Utilized HepG2 and HCCLM3 cell models of sorafenib-resistant HCC.
- Performed RPL28 knockdown using siRNA to assess effects on cell proliferation, migration, and sorafenib sensitivity (IC50).
- Conducted integrated transcriptomic and proteomic analyses to identify downstream targets and pathways, with validation by Western blotting.
Main Results:
- RPL28 expression was significantly reduced in sorafenib-resistant HCC cells following knockdown.
- RPL28 knockdown inhibited proliferation and migration in resistant HCC cells.
- CDC6 was identified as a key downstream target of RPL28, with its expression decreasing upon RPL28 knockdown; immune markers MHC-I and PD-L1 remained unchanged.
Conclusions:
- RPL28 promotes sorafenib resistance in HCC by upregulating CDC6, thereby contributing to tumor proliferation and drug resistance.
- The novel RPL28-CDC6 axis represents a significant mechanism underlying sorafenib resistance in HCC.
- Targeting the RPL28-CDC6 pathway offers a potential therapeutic strategy to overcome sorafenib resistance in advanced HCC.
Keywords:
CDC6hepatocellular carcinomaproteomeribosomal proteins L28 (RPL28)sorafenib resistancetranscriptomeMore Related Videos
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