Circular RNA hsa_circ_0006421 inhibits hepatocellular carcinoma by acting as a ceRNA targeting miR-134-5p/CELF2 pathway

Background: Hepatocellular carcinoma (HCC), ranking as the sixth most prevalent malignancy globally, exhibits substantial clinical burden. Emerging evidence underscores the critical involvement of circular RNAs (circRNAs) in the pathogenesis of various malignancies. While hsa_circ_0006421 has been implicated in gastric cancer progression, its functional significance in HCC remains unexplored. This study investigates the mechanistic role of hsa_circ_0006421 in HCC pathogenesis. Methods: Differentially expressed circRNAs in HCC tissues were identified through integrated bioinformatics analysis of the GSE97332 dataset and high-throughput sequencing of clinical specimens. Functional characterization of hsa_circ_0006421 was performed using in vitro cellular models (HepG2, MHCC97H) and xenograft experiments. Molecular interactions were validated via qRT-PCR, Western blot, and dual-luciferase reporter assays. Results: Clinical analyses revealed significant downregulation of hsa_circ_0006421 in HCC tissues, particularly in patients with cirrhosis history. Functional studies demonstrated that hsa_circ_0006421 overexpression suppressed HCC proliferation, migration, and invasion. Mechanistically, hsa_circ_0006421 functioned as a competitive endogenous RNA by sequestering miR-134-5p, thereby alleviating its inhibitory effect on CELF2 expression. A negative regulatory relationship between miR-134-5p and CELF2 was established, with hsa_circ_0006421 restoration significantly upregulating CELF2 protein levels in HCC cells. Conclusion: Our findings elucidate a novel hsa_circ_0006421/miR-134-5p/CELF2 regulatory axis that suppresses HCC progression, providing potential therapeutic targets for HCC management.