Inflammation-associated hsa_circ_0054391 regulates epithelial-mesenchymal transition and vasculogenic mimicry in colorectal cancer via the miR-1252-3p/VEGFA/ZEB1 axis

Abstract

To define the functional role of hsa_circ_0054391 (circ54391) in CRC progression and to evaluate its potential as a serum biomarker. Circ54391 was identified from databases and its expression was validated in CRC tissues, cell lines, and serum from healthy controls ( n  = 34), colorectal polyp patients ( n  = 30), and CRC patients ( n  = 69). Diagnostic performance and clinicopathological correlations were analyzed. Functional assays were performed in vitro (proliferation, migration, invasion, apoptosis, VM) and in vivo (xenograft models). Mechanistic studies focused on the circ54391/miR-1252-3p/VEGFA/ZEB1 axis. Interactions and downstream effects were assessed using FISH, qRT-PCR, Western blotting, and dual-luciferase assays. Circ54391 was highly upregulated in CRC and correlated with advanced invasion, lymph node/distant metastasis, and TNF-α levels. Serum circ54391 yielded an AUC of 0.7257 (95% CI, 0.6365–0.8150); when combined with CEA, the AUC increased to 0.8224 (95% CI, 0.7515–0.8933). Silencing circ54391 suppressed proliferation, migration, invasion, and VM in vitro and in vivo. Mechanistically, circ54391 acted as a sponge for miR-1252-3p, leading to upregulation of VEGFA and ZEB1, thereby driving EMT and VM. Circ54391 promotes CRC progression via the miR-1252-3p/VEGFA/ZEB1 axis and supports circ54391 as a serum-accessible biomarker candidate for CRC.