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Updated: Jan 21, 2026

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Discovery of core genes in colorectal cancer by weighted gene co-expression network analysis
Cun Liao1, Xue Huang2, Yizhen Gong1
1Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530000, P.R. China.
Abstract:
The aim of the present study was to investigate the interactions among messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in colorectal cancer (CRC), in order to examine its underlying mechanisms. The raw gene expression data was downloaded from the Gene Expression Omnibus (GEO) database. An online tool, GEO2R, which is based on the limma package, was used to identify differentially expressed genes. The co-expression between lncRNAs and mRNAs was identified utilizing the weighted gene co-expression analysis package of R to construct a coding non-coding (CNC) network. The function of the genes in the CNC network was determined by performing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis. The interactions among miRNAs, mRNAs and lncRNAs were predicted using Lncbase and mirWalk to construct the competing endogenous RNA (ceRNA) network. The expression of the genes involved in the ceRNA network was further validated in The Cancer Genome Atlas dataset. A total of 3,183 dysregulated mRNAs, 78 dysregulated miRNAs and 2,248 dysregulated lncRNAs were screened in two GEO datasets. Combined with the results of the dysregulated genes, 169 genes were selected to construct the CNC network. 'p53 signaling pathway' and the 'cell cycle' were the most significant enriched pathways in the genes involved in the CNC network. Finally, a validated ceRNA network composed of 2 lncRNAs (MIR22HG and RP11-61I13.3), 5 miRNAs (hsa-miR-765, hsa-miR-198, hsa-miR-125a-3p, hsa-miR-149-3p and hsa-miR-650) and 5 mRNAs (ANK2, BTK, GBP2, PCSK5 and PDK4) was obtained. In conclusion, MIR22HG may regulate PCSK5, BTK and PDK4, and RP11-61I13.3 may regulate the ANK2, GBP2, PCSK5 through sponging miRNAs to act on the progression of CRC, and the potential function of these genes have been revealed. However, the diagnostic and prognostic value of these genes requires further validation.
Insights
This study explored interactions between messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). Researchers identified key regulatory networks and potential therapeutic targets, including MIR22HG and RP11-61I13.3, offering insights into CRC mechanisms.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Colorectal cancer (CRC) progression involves complex gene regulatory networks.
- Understanding interactions among messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) is crucial for elucidating CRC mechanisms.
Purpose of the Study:
- To investigate the intricate interactions among mRNAs, miRNAs, and lncRNAs in colorectal cancer.
- To identify key regulatory networks and potential therapeutic targets in CRC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) database for raw gene expression data.
- Employed GEO2R and limma for differential gene expression analysis.
- Constructed coding non-coding (CNC) and competing endogenous RNA (ceRNA) networks using weighted gene co-expression analysis, Lncbase, and mirWalk.
- Validated findings in The Cancer Genome Atlas (TCGA) dataset.
Main Results:
- Identified 3,183 dysregulated mRNAs, 78 miRNAs, and 2,248 lncRNAs.
- Constructed a CNC network with 169 genes, highlighting 'p53 signaling pathway' and 'cell cycle' as significant pathways.
- Established a validated ceRNA network involving MIR22HG, RP11-61I13.3, five miRNAs, and five mRNAs (ANK2, BTK, GBP2, PCSK5, PDK4).
Conclusions:
- MIR22HG and RP11-61I13.3 may regulate CRC progression by sponging miRNAs and affecting target mRNAs like PCSK5, BTK, PDK4, and ANK2, GBP2.
- The study reveals potential functions of these genes in CRC.
- Further validation is needed to confirm the diagnostic and prognostic value of these identified genes.
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