Bufalin targets E2F2 to transcriptionally inhibit LINC01410 and suppress Wnt/β-catenin signaling in esophageal squamous cell carcinoma.

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.