LncRNA DLGAP1-AS2 promotes ESCC progression and indicates unfavorable prognosis via the miR-101-3p/EZH2 axis.

OBJECTIVE: LncRNAs are crucial regulators and biomarkers in various cancers. However, their expression and functions in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. This study explored the clinial relevance and mechanisms of LncRNA DLGAP1-AS2 in ESCC. METHODS: Utilizing the GEO dataset, the identification of differentially expressed lncRNAs in ESCC encompassed DLGAP1-AS2. RT-qPCR was employed to measure its expression in 135 paired tumors and adjacent non-cancerous tissue samples. Patients were followed up for five years. Kaplan-Meier curves and Cox regression analysis evaluated DLGAP1-AS2's prognostic impact, while CCK-8 and Transwell assays assessed cell proliferation. Additionally, commercial assay kits measured ROS, MDA, GSH, and iron levels. DLR and RIP assays confirmed miR-101-3p targeting DLGAP1-AS2 and EZH2. RESULTS: DLGAP1-AS2 was markedly upregulated in ESCC tumor tissues and cell lines. High expression of DLGAP1-AS2 correlated with advanced clinical stages and extensive lymph node metastasis in ESCC patients, and patients with elevated DLGAP1-AS2 expression had a worse prognosis. Mechanistically, DLGAP1-AS2 competitively binds miR-101-3p, upregulating EZH2. Depleting DLGAP1-AS2 significantly curbed ESCC cell proliferation, migration, invasion, and EMT, while boosting ferroptosis-an effect notably reversed by miR-101-3p reduction. CONCLUSION: DLGAP1-AS2 acts as a potential biomarker for unfavorable prognosis in ESCC patients. Mechanistically, it promotes malignant phenotypes of ESCC cells in vitro by regulating the miR-101-3p/EZH2 axis, enhancing proliferation and EMT, while suppressing ferroptosis.