ODF3B Promotes the Progression of Clear Cell Renal Cell Carcinoma via the JAK/STAT Signaling Pathway

BACKGROUND Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, often associated with poor prognosis due to metastasis and treatment resistance. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a major oncogenic driver in ccRCC, but its upstream regulators remain unclear. Outer dense fiber of sperm tails 3B (ODF3B), initially identified in sperm flagella, shows aberrant expression in a subset of human malignancies, and emerging transcriptomic data suggest notable dysregulation of ODF3B in ccRCC, although its functional role in this tumor type remains unknown. MATERIAL AND METHODS ODF3B expression was analyzed using data from The Cancer Genome Atlas (TCGA) and validated in ccRCC cell lines. Prognostic significance was evaluated through clinicopathological and survival analyses. Functional assays, including Cell Counting Kit 8, colony formation, wound healing, Transwell assay, and flow cytometry, were performed after ODF3B knockdown in 786-O and OSRC-2 cells. Pathway enrichment analyses and Western blotting were used to explore mechanisms, and rescue experiments were conducted with the STAT3 agonist Colivelin TFA. RESULTS ODF3B was markedly upregulated in ccRCC tissues and cells, with high expression correlating with advanced stage, metastasis, and poor survival. ODF3B silencing suppressed proliferation, migration, and invasion while enhancing apoptosis, accompanied by reduced BCL2 and increased cleaved caspase-3. Bioinformatics revealed strong enrichment of JAK/STAT signaling in tumors with high expression of ODF3B. Mechanistically, ODF3B knockdown decreased phosphorylation of JAK1/2/3 and STAT3, whereas STAT3 activation rescued proliferative and anti-apoptotic effects. CONCLUSIONS ODF3B acts as a novel oncogenic driver in ccRCC by activating JAK/STAT signaling. Its overexpression predicts aggressive features and poor prognosis, highlighting ODF3B as a potential therapeutic target.