BML-111 inhibits cervical adenocarcinoma progression via the TGF-β1–YAP1–PAICS axis

Cervical adenocarcinoma has a poorer prognosis than squamous carcinoma,with disease progression driven by epithelial–mesenchymal transition (EMT) and metabolic reprogramming. The purine synthesis enzyme phosphoribosylaminoimidazole carboxylase (PAICS) is linked to tumour progression, yet its prognostic value and upstream regulation in cervical cancer remain poorly defined.Here, we investigated PAICS as a prognostic biomarker for cervical adenocarcinoma using bioinformatics and clinical samples. We further characterised the transforming growth factor‑β1 (TGF‑β1)–Yes‑associated protein 1 (YAP1)–PAICS axis and its role in tumour progression in cervical cancer cells. We also assessed the antitumour activity of the lipoxin A4 analog BML‑111 in vitro and in vivo. Bioinformatic screening identified PAICS as a potential prognostic marker. Immunohistochemistry of 62 clinical specimens confirmed high PAICS expression, which correlated positively with YAP1 (r = 0.5675, P  < 0.001). In HeLa and SiHa cells, TGF‑β1 activated YAP1, upregulated PAICS, and promoted EMT. BML‑111 reversed these effects via formyl peptide receptor 2/lipoxin A4 (FPR2/ALX). YAP1 silencing abrogated both TGF‑β1‑mediated oncogenic effects and BML‑111‑induced protection. Xenograft studies confirmed that BML‑111 inhibited tumour growth and downregulated YAP1, PAICS and mesenchymal markers. Collectively, PAICS serves as an independent adverse prognostic factor in cervical adenocarcinoma. BML‑111 exerts robust antitumour effects by targeting the TGF‑β1–YAP1–PAICS axis, offering a promising therapeutic strategy for this disease.