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In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Integrated whole transcriptome profiling revealed a convoluted circular RNA-based competing endogenous RNAs
Hasan Mollanoori1, Yaser Ghelmani2, Bita Hassani3
1Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Abstract:
Recently, it has been identified that circRNAs can act as miRNA sponge to regulate gene expression in various types of cancers, associating them with cancer initiation and progression. The present study aims to identify colorectal cancer-related circRNAs and the underpinning mechanisms of circRNA/miRNA/mRNA networks in the development and progress of Colorectal Cancer. Differentially expressed circRNAs, miRNAs, and mRNAs were identified in GEO microarray datasets using the Limma package of R. The analysis of differentially expressed circRNAs resulted in 23 upregulated and 31 downregulated circRNAs. CeRNAs networks were constructed by intersecting the results of predicted and experimentally validated databases, circbank and miRWalk, and by performing DEMs and DEGs analysis using Cytoscape. Next, functional enrichment analysis was performed for DEGs included in ceRNA networks. Followed by survival analysis, expression profile assessment using TCGA and GEO data, and ROC curve analysis we identified a ceRNA sub-networks that revealed the potential regulatory effect of hsa_circ_0001955 and hsa_circ_0071681 on survival-related genes, namely KLF4, MYC, CCNA2, RACGAP1, and CD44. Overall, we constructed a convoluted regulatory network and outlined its likely mechanisms of action in CRC, which may contribute to the development of more effective approaches for early diagnosis, prognosis, and treatment of CRC.
Insights
Circular RNAs (circRNAs) regulate gene expression in cancer. This study identifies colorectal cancer-related circRNAs and their regulatory networks, revealing potential diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- circRNAs can function as miRNA sponges, influencing gene expression and impacting cancer initiation and progression.
Purpose of the Study:
- To identify circRNAs associated with colorectal cancer (CRC).
- To elucidate the molecular mechanisms of circRNA/miRNA/mRNA networks in CRC pathogenesis.
- To discover potential biomarkers for CRC diagnosis and treatment.
Main Methods:
- Analysis of differentially expressed circRNAs, miRNAs, and mRNAs from GEO microarray datasets.
- Construction of circRNA/miRNA/mRNA ceRNA networks using Cytoscape.
- Functional enrichment analysis, survival analysis, and ROC curve analysis using TCGA and GEO data.
Main Results:
- Identified 23 upregulated and 31 downregulated circRNAs in CRC.
- Constructed complex ceRNA networks, highlighting specific circRNAs (hsa_circ_0001955, hsa_circ_0071681).
- Identified a ceRNA sub-network implicating these circRNAs in regulating survival-related genes (KLF4, MYC, CCNA2, RACGAP1, CD44).
Conclusions:
- A comprehensive regulatory network in CRC was established.
- The identified circRNAs and their networks offer potential for novel CRC diagnostic, prognostic, and therapeutic strategies.
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