Abstract
A large proportion of liver cancer cases is caused by hepatitis B virus (HBV) infection. In recent years, an increasing number of reports have indicated that circular RNAs (circRNAs) exert regulatory effects in cancer development, whereas the role of circRNAs in HBV-positive liver cancer requires further investigation. In the present study, abnormally expressed circRNAs were identified in HBV-positive liver cancer cells through microarray analysis. A total of 1,493 differentially expressed circRNAs [absolute fold-change (FC) ≥2] in HBV-positive liver cancer cells were detected, of which 171 were upregulated and 1,322 were downregulated. Subsequently, Gene Ontology enrichment analysis indicated that the genes of dysregulated circRNAs were mainly involved in regulating Sertoli cell differentiation and development, as well as telomeric DNA binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that most of these genes were enriched in cancer-related signaling pathways, including the MAPK and Hippo signaling pathways. Next, the expression levels of the top-10 dysregulated circRNAs were verified in HBV-positive liver cancer cells through reverse transcription-quantitative PCR. Among them, hsa_circ_0066966 had the highest absolute Log2FC value and was abnormally increased in HBV-positive liver cancer cells. Functional experiments further verified that knockdown of hsa_circ_0066966 had a significant inhibitory effect on the proliferation and migration of HBV-positive liver cancer cells. By contrast, overexpression of hsa_circ_0066966 in HBV-negative liver cancer cells resulted in the opposite effect. In conclusion, in the present study, comprehensive circRNA profiling in HBV-positive liver cancer cells indicated that hsa_circ_0066966 may regulate the progression of HBV-positive liver cancer.