lncRNA LINC00958 Activates NOTCH3 by Competitively Inhibiting miR‐129‐2‐3p to Exacerbate the Malignant Biological Behaviors of Endometrial Cancer Cells

ABSTRACT Endometrial cancer (EC) is one of the most prevalent gynecologic malignancies, with increasing incidence worldwide. Recent studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in regulating tumor progression. This study investigated the oncogenic function of lncRNA LINC00958 in EC and its underlying mechanism involving the miR‐129‐2‐3p/NOTCH3 signaling axis. Experimental results showed that LINC00958 was significantly upregulated in EC cell lines. Overexpression of LINC00958 enhanced cell proliferation, migration, and invasion, while inhibiting apoptosis, as evidenced by increased Bcl‐2 and decreased cleaved caspase‐3 and Bax expression. Conversely, silencing LINC00958 suppressed these malignant behaviors. Mechanistically, LINC00958 acted as a competing endogenous RNA (ceRNA), directly binding to miR‐129‐2‐3p and thereby relieving its suppression on NOTCH3. Dual‐luciferase reporter assays confirmed the direct interaction between LINC00958 and miR‐129‐2‐3p, as well as between miR‐129‐2‐3p and NOTCH3. Immunofluorescence analysis further demonstrated enhanced nuclear translocation of NOTCH3 following LINC00958 overexpression. Functional rescue experiments showed that miR‐129‐2‐3p overexpression or NOTCH3 knockdown effectively counteracted the tumor‐promoting effects of LINC00958. In vivo xenograft experiments using Ishikawa cells supported the in vitro findings, confirming that LINC00958 promotes tumor growth by modulating the miR‐129‐2‐3p/NOTCH3 axis. Overall, this study identifies LINC00958 as a novel oncogenic lncRNA in EC, which facilitates tumor progression by sponging miR‐129‐2‐3p and enhancing NOTCH3 signaling. These findings provide new insights into the molecular mechanisms of EC and suggest that targeting the LINC00958/miR‐129‐2‐3p/NOTCH3 axis may represent a promising therapeutic strategy.