SEZ6L2 Promotes Cervical Carcinogenesis by Activating the Wnt Signaling Pathway

This study aimed to investigate the biological function and molecular mechanisms of seizure-related 6 homolog-like 2 (SEZ6L2) in Cervical Cancer (CC) progression and evaluated its potential as a therapeutic target.

SEZ6L2 expression was analyzed in CC tissues and cells using online tools and experimental validation. Functional experiments, including cell-counting Kit-8, colony formation, wound-healing, transwell, and flow cytometry, together with in vivo models, were performed to assess the effects of SEZ6L2 on proliferation, migration, and metastasis. GSEA and Metascape enrichment were used to identify associated pathways. TargetScan was used to predict upstream miRNAs, followed by validation with dual-luciferase assays.

SEZ6L2 was significantly overexpressed in CC and correlated with poor prognosis. Knockdown of SEZ6L2 inhibited CC proliferation, migration, and invasion while inducing cell cycle arrest. In vivo, SEZ6L2 silencing reduced tumor growth and metastasis. Mechanistically, SEZ6L2 was found to activate the Wnt/β-catenin pathway, leading to upregulating β-catenin and driving Epithelial-Mesenchymal Transition (EMT). GSEA confirmed the involvement of the Wnt pathway. Moreover, hsa-miR1271-5p was identified as a direct upstream regulator of SEZ6L2.

Our findings identified SEZ6L2 as a novel oncoprotein in CC, contributing to tumor pathogenesis by activating the Wnt/β-catenin signaling and promoting EMT-driven metastasis. We further demonstrated that hsa-miR-1271-5p acts as a direct upstream repressor, providing mechanistic insight into the regulatory network governing SEZ6L2 expression. Collectively, these results position SEZ6L2 as a robust prognostic biomarker and illuminate its potential as a therapeutic target.

SEZ6L2 promotes CC progression via Wnt/β-catenin signaling and EMT, serving as a prognostic biomarker and therapeutic target. Hsa-miR1271-5p may suppress SEZ6L2 expression, offering novel insights for CC treatment strategies.