Long non-coding RNA HOXC-AS1 promotes the malignancy by sponging miR-195-5p with ANLN in esophageal cancer

Abstract

Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) exhibits elevated expression in gastric and prostate cancers, yet its involvement in esophageal cancer (EC) remains unexplored. This investigation assessed the expression patterns and functional implications of HOXC-AS1 in EC. Quantitative real-time PCR was employed to evaluate HOXC-AS1 expression in EC cell lines, while its impact on cell proliferation, migration, invasion, tumor growth, and metastasis was examined through MTT, EdU, transwell, wound healing assays, and animal models. Mechanistic insights into HOXC-AS1 were pursued using dual-luciferase reporter assays and RNA immunoprecipitation. Analysis of TCGA data demonstrated significant upregulation of HOXC-AS1 in EC tissues, consistent with its enriched expression in EC cell lines. Knockdown experiments revealed that suppressing HOXC-AS1 reduced proliferation, migration, and invasion of EC cells in vitro and inhibited tumor growth and metastasis in vivo. Mechanistically, HOXC-AS1 acted as a molecular sponge for miR-195-5p, with anillin actin-binding protein (ANLN) identified as a direct downstream target of miR-195-5p. Functional rescue experiments showed that inhibiting miR-195-5p or overexpressing ANLN counteracted the suppressive effects induced by HOXC-AS1 silencing on the aggressive phenotypes of EC cells. These findings establish HOXC-AS1 as a promoter of EC progression via regulation of the miR-195-5p/ANLN axis, suggesting its utility as a prospective therapeutic target for EC management.

Keywords: ANLN; Esophageal cancer; HOXC-AS1; Invasion; Migration; Proliferation; miR-195-5p.