CircUBAP2 promotes intrahepatic cholangiocarcinoma progression via PRMT1-p65 methylation and the miR-642b-5p/IL-1β axis.

Intrahepatic cholangiocarcinoma (ICC) frequently exhibits inflammatory signaling and poor outcomes, yet upstream regulators that maintain NF-κB activity remain incompletely defined. Here, we identified circUBAP2 (hsa_circ_0001851) by circRNA microarray and validated it in 76 paired ICC tissues and cell lines. Higher circUBAP2 levels were associated with advanced stage and poorer survival. Gain- and loss-of-function assays showed that circUBAP2 enhanced proliferation and migration in vitro and promoted tumor growth and liver metastasis in vivo, accompanied by increased NF-κB activity. Biotinylated RNA pull-down coupled with mass spectrometry and RIP confirmed an interaction between circUBAP2 and PRMT1, which was accompanied by reduced PRMT1-p65 association and decreased inhibitory p65 R30 dimethylation. PRMT1 ChIP-seq further revealed altered chromatin occupancy and motif enrichment in circUBAP2-overexpressing cells, with NF-κB motifs no longer among the top enriched motifs. In parallel, circUBAP2 sponged miR-642b-5p, thereby relieving miR-642b-5p-mediated repression of IL1B and increasing IL-1β expression. Pharmacologic IL-1 receptor blockade with anakinra attenuated circUBAP2-associated tumor growth in vivo. Collectively, these data identify circUBAP2 as a candidate prognostic biomarker and suggest that IL-1-targeted strategies warrant evaluation in circUBAP2-high ICC.