Related Experiment Videos
CircUBAP2 promotes intrahepatic cholangiocarcinoma progression via PRMT1-p65 methylation and the miR-642b-5p/IL-1β
Chang Li1, Shuochen Liu1, Changan Chen1
1Hepatobiliary Center, The First Affiliated Hospital with Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu Province, China.
Abstract:
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.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
PI3K/mTOR/AKT Signaling Pathway
Induced Pluripotent Stem Cells
Somatic cells are...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...