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

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Circular RNAs (circRNAs) play a role in cancer development, with altered expression observed in hepatocellular carcinoma (HCC).
• Mechanisms regulating circRNA expression in HCC remain largely unknown.
• Understanding circRNA regulation is crucial for identifying novel therapeutic targets in HCC.

Purpose of the Study:

• To identify RNA binding proteins (RBPs) that regulate circRNAome expression in hepatocellular carcinoma (HCC).
• To investigate the role of specific RBPs, such as epithelial splicing regulatory protein 2 (ESRP2), in circRNA regulation in HCC.

Main Methods:

• Analysis of publicly available gene expression datasets to identify RBPs with enriched motifs near differentially expressed circRNAs in HCC.
• Validation of RBP binding using ChIP-seq and eCLIP data from the ENCODE database.
• Experimental validation by knocking down ESRP2 in an HCC cell line to assess its impact on candidate circRNA expression.

Main Results:

• Several RBPs, including NONO, PCPB2, PCPB1, ESRP2, and HNRNPK, were identified as candidate regulators of circRNA expression in HCC.
• Some identified RBPs were differentially expressed in HCC and/or correlated with patient survival.
• Knockdown of ESRP2 significantly altered the expression of specific circRNAs in an HCC cell line model.

Conclusions:

• NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are proposed as key regulators of circRNA expression in HCC.
• ESRP2 plays a significant role in regulating circRNA expression in HCC.
• Identifying regulators of circRNAome changes provides insights into molecular pathways driving HCC development and offers potential therapeutic strategies.