Berberine alleviates the proliferation and metastasis of ESCA by promoting CCDC18-AS1 expression based on bioinformatics and in vitro experimental verification.

Although berberine exhibits anticancer activity, its mechanistic role in esophageal cancer (ESCA) remains unclear. Long non-coding RNAs (lncRNAs) expression profiling was conducted on berberine-treated and control ESCA TE-1 cells, identifying differentially expressed lncRNAs. Prognostic lncRNAs were selected through integration with the TCGA database, followed by the construction of a prognostic nomogram. In vitro assays and bioinformatics analyses were performed to validate berberine's impact on cell proliferation, metastasis, and key lncRNAs. Berberine treatment significantly altered lncRNA expression in TE-1 cells, with 344 upregulated and 235 downregulated lncRNAs. The expression of CCDC18-AS1, TBILA, and LINC02084 was associated with poorer overall survival (OS) and served as independent prognostic factors in ESCA. The nomogram accurately predicted 1-, 3-, and 5-year OS rates. Berberine inhibited TE-1 cell proliferation, migration, and invasion, primarily through the upregulation of CCDC18-AS1 expression. Genes co-expressed with CCDC18-AS1 were enriched in mRNA processing, RNA splicing, spliceosome, and mRNA surveillance pathways. Among these, overexpression of PCMTD2 and AL391840.2 represented risk factors, while RBM43 and LRIG2 were identified as protective factors in ESCA. Berberine may inhibit ESCA progression by modulating CCDC18-AS1 expression, thereby improving patient prognosis.