Knockdown of RPL28 Inhibits the Progression of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histological subtype of kidney cancer. Previous studies have implicated ribosomal protein L28 (RPL28) in the progression of various cancers; however, its role in ccRCC remains unclear. AIMS: This study aimed to investigate the expression, prognostic significance, and potential biological role of RPL28 in ccRCC. METHODS AND RESULTS: RPL28 expression data and corresponding clinicopathological information were obtained from the UCSC Xena platform, and pan-cancer expression patterns were assessed using TIMER2.0. RPL28 expression was further validated in clinical ccRCC tissue samples. Prognostic, immune-infiltration, and drug-sensitivity analyses were performed, and the biological effects of RPL28 were evaluated using lentivirus-mediated knockdown in ccRCC cells. RPL28 was significantly upregulated in ccRCC tissues and was associated with unfavorable overall survival (OS) and disease-specific survival (DSS), as well as adverse clinicopathological features, including higher histological grade, advanced T stage, distant metastasis, and advanced TNM stage. Immune analyses revealed associations between RPL28 expression and selected features of the ccRCC immune microenvironment, while pharmacogenomic analyses suggested potential associations between RPL28 expression and predicted sensitivity to selected targeted agents. In vitro, RPL28 knockdown significantly inhibited ccRCC cell proliferation and migration. Gene set enrichment analysis (GSEA), together with experimental findings, further suggested that RPL28 may be involved in epithelial-mesenchymal transition (EMT)-related processes in ccRCC. CONCLUSION: RPL28 is overexpressed in ccRCC and is associated with poor survival outcomes, malignant cellular phenotypes, EMT-related signaling, selected immune-microenvironmental features, and predicted therapeutic-response phenotypes. These findings suggest that RPL28 may serve as a prognostic biomarker and potential therapeutic target in ccRCC, although further mechanistic and clinical validation is required.