The novel role of APOBEC3C in mediating NF-kB activation to enhance clear cell renal cell carcinoma progression

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and often lacks effective therapies, particularly in metastatic stages. This study identifies the RNA-binding protein APOBEC3C (A3C) as significantly upregulated in ccRCC, especially in advanced stages, correlating with poor patient survival. Functional analyses, including RNA sequencing, qPCR, Western blotting, and cell-based assays in ccRCC-derived cell lines with altered A3C levels, reveal that A3C promotes NF-κB signaling. A3C interacts with transcripts of positive NF-κB regulators, potentially affecting their stability or translation, thereby enhancing NF-κB activity and tumor growth. This effect is independent of A3C’s cytidine deaminase function, suggesting a novel regulatory mechanism. A3C also supports tumor cell viability under stress, highlighting its role in survival pathways. These findings position A3C as a key driver of ccRCC progression and a promising therapeutic target.