Related Experiment Video
Updated: Jun 28, 2026
Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
Published on: October 3, 2025
Comprehensive analysis of the RBP regulome reveals functional modules and drug candidates in liver cancer
Mateusz Garbulowski1,2, Riccardo Mosca3, Carlos J Gallardo-Dodd3
1Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden. mateusz.garbulowski@scilifelab.se.
Abstract:
RNA binding proteins (RBPs) are essential components of the transcriptomic regulome. Understanding the RBP regulome in cancer cells is crucial for uncovering carcinogenesis mechanisms and identifying novel therapeutic targets. In this study, we aimed to reveal the regulome of liver cancer upon specific perturbations. To achieve this, we applied a consensus Gene Regulatory Network (GRN) approach using knockdown data focusing on the liver cancer cell line HepG2. By integrating multiple GRNs inferred from diverse computational methods, we constructed a comprehensive regulatory network. To validate our findings, we evaluated the consensus GRN by focusing on characterizing key regulatory interactions in liver cancer. We used eCLIP-seq and RAP-seq data to verify RBP interactions and binding sites. In addition, we performed an enrichment analysis of network modules and in silico drug repurposing based on the inferred GRN. Taken together, our findings highlight the critical role of RBP-mediated regulation in liver cancer, which can be used to improve treatment strategies and develop further research.
Insights
This study reveals the critical role of RNA binding proteins (RBPs) in liver cancer by constructing a comprehensive gene regulatory network (GRN). Findings offer new therapeutic targets for liver cancer treatment.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- RNA binding proteins (RBPs) are key regulators of gene expression.
- Understanding the RBP regulome is vital for deciphering cancer development and finding new treatments.
Purpose of the Study:
- To elucidate the liver cancer RBP regulome using a consensus Gene Regulatory Network (GRN) approach.
- To identify key regulatory interactions and potential therapeutic targets in liver cancer.
Main Methods:
- Applied a consensus GRN approach integrating multiple computational methods with HepG2 cell line knockdown data.
- Validated RBP interactions and binding sites using eCLIP-seq and RAP-seq data.
- Performed network module enrichment analysis and in silico drug repurposing.
Main Results:
- Constructed a comprehensive regulatory network for liver cancer.
- Identified critical RBP-mediated regulatory interactions.
- Validated RBP binding sites and interactions through experimental data.
- Identified potential drug candidates through in silico analysis.
Conclusions:
- RBPs play a crucial role in liver cancer regulation.
- The constructed GRN provides insights into carcinogenesis mechanisms.
- Findings can inform improved liver cancer treatment strategies and future research directions.
