Identification of novel RNA binding proteins influencing circular RNA expression in hepatocellular carcinoma

Razpotnik, Rok (author), Nassib, Petra (author), Kunej, Tanja (author), Rozman, Damjana (author), Režen, Tadeja (author)

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.

• Language: English
• Keywords: hepatocellular carcinoma (HCC), circular RNA (circRNA), identification of novel proteins, RNA binding proteins (RBPs), ESRP2
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 14 str.
• Numbering: Vol. 22, iss. 14, art. 7477
• PID: 20.500.12556/RUL-135591
• UDC: 616-006
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22147477
• COBISS.SI-ID: 70157827
• Publication date in RUL: 21.03.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 12.07.2021

Secondary language

• Language: Slovenian
• Keywords: hepatocelularni karcinom, krožna RNA, identifikacija novih proteinov