Endometrial cancer (EC) is a prevalent gynecological malignancy with a rising incidence and poor prognosis in advanced cases. Long non-coding RNAs (lncRNAs) have been implicated in various cancers, including EC. This study explores the role of lncRNA Linc01224 in EC. Analyzing TCGA data, we found Linc01224 expression significantly elevated in EC tissues, correlating with poor prognosis. Clinical samples validated these findings, showing higher Linc01224 levels in tumor tissues. Knockdown of Linc01224 in EC cell lines (Hec-1-B and Ishikawa) inhibited proliferation, migration, and promoted apoptosis, alongside increased Bax and decreased BCL2 expression. Furthermore, Linc01224 knockdown notably reduced Wnt2/β-catenin pathway activation. We identified TPX2 as a target of miR-4673, which is regulated by Linc01224 through a competing endogenous RNA (ceRNA) mechanism. Dual-luciferase reporter assays confirmed miR-4673 binding to Linc01224 and TPX2. Rescue experiments revealed that TPX2 knockdown reversed Linc01224-induced proliferation and migration, highlighting TPX2's pivotal role in Linc01224's oncogenic function. In vivo, Linc01224 knockdown significantly impeded tumor growth and metastasis in a xenograft model, with decreased expression of c-Myc, Cyclin D1, and β-catenin. These findings reveal a novel ceRNA regulatory axis involving Linc01224, miR-4673, and TPX2, elucidating Linc01224's role in EC progression through the Wnt2/β-catenin pathway. Linc01224 emerges as a potential biomarker and therapeutic target for EC prognosis and treatment.
Keywords: Linc01224; TPX2; Wnt2/β‐catenin pathway; endometrial cancer; miR‐4673.
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