Bufalin targets E2F2 to transcriptionally inhibit LINC01410 and suppress Wnt/β-catenin signaling in esophageal squamous cell carcinoma
Menée à l'aide de lignées cellulaires, de modèles murins de carcinome épidermoïde de l'oesophage et d'un modèle d'apprentissage automatique, cette étude met en évidence un mécanisme par lequel la bufaline, en induisant la dégradation du facteur de transcription E2F2, supprime la croissance tumorale et le développement de métastases via l'inhibition de la transcription du long ARN non codant LINC01410 ainsi que la suppression de la signalisation de la voie Wnt/bêta-caténine
Bufalin, a main active monomer component extracted from the Traditional Chinese Medicine toad venom, exhibits potent anti-tumour activity across diverse malignancies. However, its specific molecular targets in Oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, we demonstrate that bufalin suppresses ESCC growth and metastasis in a concentration-dependent manner both in vitro and in vivo. RNA sequencing analysis revealed that bufalin inhibits ESCC progression by downregulating LINC01410. TCGA-ESCC data indicated that LINC01410 is highly expressed in ESCC tissues and promotes tumour progression by stabilising β-catenin protein and activating the Wnt/β-catenin pathway. Through multiple approaches including proteome microarray screening and machine learning analyses, we identified E2F2 as a upstream transcription factor of LINC01410. We further demonstrate that bufalin induces the proteasomal degradation of E2F2, consequently silencing LINC01410 transcription and collapsing the LINC01410-Wnt/β-catenin signalling axis. In summary, our findings indicate that bufalin targets E2F2 to downregulate LINC01410, thereby providing a potential therapeutic strategy for suppressing ESCC progression.
npj Precision Oncology , article en libre accès, 2026