Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

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...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (14), p.7477
Main Authors: Razpotnik, Rok, Nassib, Petra, Kunej, Tanja, Rozman, Damjana, Režen, Tadeja
Format: Article
Language:English
Subjects:
Binding
Binding sites
Bioinformatics
Biomarkers
Biosynthesis
Circular RNA
circular RNA (circRNA)
Datasets
ESRP2
Gene expression
Hepatocellular carcinoma
hepatocellular carcinoma (HCC)
Liver cancer
Patients
Phenotypes
Proteins
RNA binding proteins (RBPs)
RNA-binding protein
Splicing
Transcriptomes
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22147477