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Updated: Feb 6, 2026
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of
Dan-Dan Xiong1, Yi-Wu Dang1, Peng Lin2
1Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Background:
Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC).
Methods:
A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC.
Results:
Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA-miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein-protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis.
Conclusions:
Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.
Insights
This study uncovers novel circular RNAs (circRNAs) and their mechanisms in hepatocellular carcinoma (HCC). It identifies key genes and potential therapeutic agents, offering new insights into HCC pathogenesis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their role in human cancers.
- Many circRNAs in hepatocellular carcinoma (HCC) remain uncharacterized.
- This study aims to identify novel circRNAs and elucidate their functional mechanisms in HCC.
Purpose of the Study:
- To discover novel circRNAs involved in hepatocellular carcinoma (HCC).
- To explore the action mechanisms of these circRNAs in HCC.
- To identify potential therapeutic agents for HCC based on molecular interactions.
Main Methods:
- Utilized big data mining, RT-qPCR, and computational biology to identify HCC-related circRNAs.
- Employed RobustRankAggreg method on microarray datasets (GSE78520, GSE94508, GSE97332) to find differentially expressed circRNAs.
- Constructed a circRNA-miRNA-mRNA network and performed Connectivity Map (CMap) analysis for therapeutic targets.
Main Results:
- Identified three key circRNAs (hsa_circRNA_102166, hsa_circRNA_100291, hsa_circRNA_104515) and their interactions with five miRNAs.
- Established a protein-protein interaction network revealing seven hub genes (JUN, MYCN, AR, ESR1, FOXO1, IGF1, CD34) crucial for HCC pathogenesis.
- Discovered three potential therapeutic agents (decitabine, BW-B70C, gefitinib) for HCC through CMap analysis.
Conclusions:
- The study elucidates the circRNA-miRNA-mRNA network in HCC pathogenesis.
- Identified novel circRNAs and hub genes provide a deeper understanding of HCC.
- The findings suggest potential novel therapeutic strategies for hepatocellular carcinoma.
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