Long non-coding RNA HOXC-AS3 promotes proliferation and metastasis of esophageal squamous carcinoma by targeting WNT3A through binding to YBX1.

Esophageal squamous cell carcinoma (ESCC) is one of the malignancies with high morbidity and mortality rates. Previous studies have demonstrated the critical roles of long non-coding RNAs (lncRNAs) in cell differentiation, embryonic development and cancer progression. The lncRNA HOXC-AS3 has been shown to exert pro-carcinogenic effects in adenocarcinoma, gastric cancer and breast cancer; however, its biological function in ESCC remains unclear. In the present study, HOXC-AS3 expression was found to be elevated in ESCC tissues. We discovered that HOXC-AS3 regulates the proliferation and migration of ESCC cells. Flow cytometry assays indicated that knockdown of HOXC-AS3 led to increased apoptosis and cell cycle arrest in ESCC cells. RNA sequencing and Gene Ontology findings revealed that the downstream genes regulated by HOXC-AS3 were primarily enriched in signaling pathways associated with cell proliferation and migration. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (CHIP) experiments confirmed that HOXC-AS3 can be recruited to the promoter region of the WNT3A gene by binding to YBX1. These findings provide evidence of lncRNA HOXC-AS3 functions as a novel oncogene in ESCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-026-15672-5.