Ribosomal protein L6 suppresses hepatocellular carcinoma by modulating FBXO22-mediated p53 degradation

The ribosomal protein L6 (RPL6) is significant in the progression of different cancer types. However, its precise role in hepatocellular carcinoma (HCC) remains unclear. This research demonstrated that the expression levels of RPL6 are notably decreased in HCC tissues. The decreased expression of RPL6 is strongly linked to tumor size, the presence of vascular invasion, and a worse prognosis. Functional experiments revealed that the expression of RPL6 impedes the proliferation of HCC cells and the advancement of xenograft tumors. Mechanistically, we found that RPL6 binds to and is degraded by the E3 ubiquitin ligase FBXO22, thereby inhibiting the polyubiquitination and subsequent degradation of p53 by FBXO22. The enhanced activity of p53 further contributes to cell growth inhibition. In contrast, the levels of p53 decreased significantly following RPL6 depletion, indicating that RPL6 is essential for the stabilization of p53. In summary, RPL6 inhibits the proliferation of HCC cells via the FBXO22/p53 signaling pathway, suggesting its potential as a biomarker and a therapeutic target for HCC. •The expression of RPL6 is negatively correlated with tumor size, proliferation, and prognosis in patients with HCC.•The E3 ubiquitin ligase FBXO22 interacts with RPL6, facilitating its degradation through K48-associated ubiquitination.•RPL6 can inhibit the ubiquitination and subsequent degradation of p53 by FBXO22 in HCC, thereby stabilizing p53.