Abstract
This study aimed to investigate the expression and evaluate the function of long non-coding RNA (LncRNA) HOXA11-AS in Esophageal Squamous Cell Carcinoma (ESCC). HOXA11-AS expression was quantified in paired ESCC tumor tissues (n = 50) and adjacent histologically normal tissues (> 5 cm from tumor margin) (n=50) from surgical patients. The relationship between HOXA11-AS expression levels, clinical staging and patient survival was analyzed. Lentiviral transduction was employed to generate stable ESCC cell lines with HOXA11-AS overexpression (lv-HOXA11-AS) or knockdown (sh-HOXA11-AS), accompanied by negative control groups (lv-NC/sh-NC). The impact on malignant phenotype was assessed via CCK-8 proliferation assays, Transwell migration/invasion assays, wound healing assays, and flow cytometry for apoptosis. In vivo tumor growth was evaluated by subcutaneously injecting fluorescently labeled lv-HOXA11-AS or lv-NC cells into BALB/c-nu mice. RNA-sequencing and tissue qRT-PCR confirmed significantly higher HOXA11-AS expression in ESCC versus normal epithelium, and high HOXA11-AS expression was associated with advanced tumor stage and was identified as an independent predictor of poor prognosis. qRT-PCR validated the elevated expression of HOXA11-AS in ESCC cell lines too. HOXA11-AS overexpression promoted proliferation, migration, invasion, and suppressed early apoptosis in ESCC cells, HOXA11-AS knockdown exerted opposing effects. HOXA11-AS overexpression significantly enhanced tumor growth in mouse xenograft models. LncRNA HOXA11-AS is aberrantly overexpressed in ESCC and functions as an oncogene, driving tumor progression by enhancing proliferation, migration, invasion and suppressing apoptosis. Its association with poor prognosis identifies HOXA11-AS as a promising prognostic biomarker and potential therapeutic target for ESCC.