ArticleBMC cancer2025
PCBP1-AS1 facilitates liver metastasis in pancreatic cancer by modulating miR-125b-5p in Tumor-derived exosomes to target TNFAIP3.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTo investigate the role of PCBP1-AS1 in pancreatic cancer (PCa) liver metastasis and its underlying mechanisms.
methodsWe analyzed the expression patterns of PCBP1-AS1, miR-125b-5p, and TNFAIP3 in PCa tissues, normal tissues, and peripheral blood exosomes. The relationships between these molecules and PCa pathological features, including liver metastasis, were examined. Dual-luciferase reporter assays confirmed the targeting interactions among PCBP1-AS1, miR-125b-5p, and TNFAIP3. We constructed PCa cell lines overexpressing miR-125b-5p and/or TNFAIP3, as well as PCBP1-AS1 and/or miR-125b-5p, to assess their effects on TNFAIP3 expression and cellular behaviors. The impact of exosomes from transfected or untransfected PCa cells on TNFAIP3 levels, NF-κB activation, and hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) transformation was evaluated. A PCa liver metastasis model was constructed to study the effects of exosomes on HSCs activation.
resultsMiR-125b-5p was largely upregulated in PCa tissues and peripheral blood exosomes, with high expression correlating with advanced disease stage and liver metastasis. MiR-125b-5p promoted PCa progression by targeting TNFAIP3. Overexpression of miR-125b-5p further enhanced TNFAIP3 suppression, p-p65 activation, and HSCs-to-CAFs transformation induced by PCa-derived exosomes, while miR-125b-5p inhibition reversed these effects. Preconditioning with PCa-derived exosomes facilitated liver metastasis in vivo, with increased miR-125b-5p levels exacerbating metastasis by targeting TNFAIP3 and activating NF-κB. Reduced PCBP1-AS1 expression was associated with poorer survival in PCa patients and was significantly lower in tissues from patients with liver metastases. PCBP1-AS1 counteracted miR-125b-5p-mediated TNFAIP3 suppression and mitigated the tumor-promoting effects of miR-125b-5p.
conclusionsPCBP1-AS1 enhances TNFAIP3 expression by targeting miR-125b-5p, thereby inhibiting PCa progression. Reduced PCBP1-AS1 in PCa increases miR-125b-5p levels in exosomes, activating NF-κB and promoting HSCs-to-CAFs transformation, creating a favorable microenvironment for liver metastasis.
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