1. Identification of novel RNA binding proteins influencing circular RNA expression in hepatocellular carcinoma
- Author
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Petra Nassib, Tanja Kunej, Tadeja Režen, Damjana Rozman, and Rok Razpotnik
- Subjects
0301 basic medicine ,identifikacija novih proteinov ,RNA-binding protein ,Apoptosis ,Transcriptome ,hepatocellular carcinoma (HCC) ,0302 clinical medicine ,Tumor Cells, Cultured ,Gene Regulatory Networks ,Biology (General) ,Spectroscopy ,Regulation of gene expression ,Liver Neoplasms ,RNA-Binding Proteins ,RNA binding proteins (RBPs) ,General Medicine ,Prognosis ,Phenotype ,identification of novel proteins ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,RNA splicing ,ESRP2 ,hepatocelularni karcinom ,Carcinoma, Hepatocellular ,QH301-705.5 ,circular RNA (circRNA) ,krožna RNA ,Computational biology ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Circular RNA ,medicine ,Biomarkers, Tumor ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,Cell Proliferation ,udc:616-006 ,Gene Expression Profiling ,Organic Chemistry ,Computational Biology ,RNA, Circular ,medicine.disease ,digestive system diseases ,MicroRNAs ,030104 developmental biology ,Cell culture - Abstract
Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC), however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.
- Published
- 2022