Circular RNA hsa_circ_0062682 Binds to YBX1 and Promotes Oncogenesis in Hepatocellular Carcinoma

SIMPLE SUMMARY: Circular RNA (circRNA) have a role in carcinogenesis in different cancers, also in hepatocellular carcinoma (HCC). The transcriptome analyses of HCC tumours identified an upregulated circRNA hsa_circ_0062682. We show that this circRNA affects several aspects of oncogenesis, which are cell proliferation, migration, and invasion. Using transcriptome analyses we identified modulated signalling pathways and transcription factors, confirming the observed phenotype in cells. We identified Y-box-binding protein 1 (YBX1), a known oncogene and RNA-binding protein, as a binding partner, which was in line with transcriptome analyses. We also identified a cell-specific response to sorafenib after circRNA modulation, which is in line with a heterogeneous molecular pathology of HCC subtypes. ABSTRACT: Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). By implementing available transcriptomic analyses of HCC patients, we identified an upregulated circRNA hsa_circ_0062682. Stable perturbations of hsa_circ_0062682 in Huh-7 and SNU-449 cell lines influenced colony formation, migration, cell proliferation, sorafenib sensitivity, and additionally induced morphological changes in cell lines, indicating an important role of hsa_circ_0062682 in oncogenesis. Pathway enrichment analysis and gene set enrichment analysis of the transcriptome data from hsa_circ_0062682 knockdown explained the observed phenotypes and exposed transcription factors E2F1, Sp1, HIF-1α, and NFκB1 as potential downstream targets. Biotinylated oligonucleotide pulldown combined with proteomic analyses identified protein interaction partners of which YBX1, a known oncogene, was confirmed by RNA immunoprecipitation. Furthermore, we discovered a complex cell-type-specific phenotype in response to the oncogenic potential of hsa_circ_0062682. This finding is in line with different classes of HCC tumours, and more studies are needed to shed a light on the molecular complexity of liver cancer.