CircIQGAP1-CARM1 axis promotes renal cell carcinoma progression through glycolytic reprogramming

Renal cell carcinoma (RCC) relies heavily on aerobic glycolysis for rapid proliferation and metastasis; however, the role of circular RNAs (circRNAs) in this process remains unclear. This study identified circIQGAP1 as a key regulator; its expression was upregulated under glucose deficiency, with U2AF2 promoting its biosynthesis. Functional assays showed that circIQGAP1 enhances RCC cell proliferation, motility, invasion, and glycolytic flux. Mechanistically, circIQGAP1 binds to CARM1, inhibiting its K48-linked ubiquitination and prolonging its half-life. Elevated CARM1 then catalyses COL5A1 promoter dimethylation, driving COL5A1 transcription. Rescue experiments confirmed that both CARM1 and COL5A1 were essential for circIQGAP1-mediated metabolic reprogramming and malignant phenotypes. Clinically, circIQGAP1 is overexpressed in RCC tissues and is correlated with poor outcomes. These findings revealed that circIQGAP1 promotes glycolysis-dependent RCC progression by stabilizing CARM1 to activate COL5A1, highlighting that this regulatory axis may provide an innovative strategy for RCC treatment.