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Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA-miRNA-mRNA in Colorectal Carcinogenesis
Jingwei Liu1, Hao Li1, Bowen Zheng1
1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, 155# North Nanjing Street, Heping District, Shenyang City, 110001, Liaoning Province, China.
Background:
Competitive endogenous RNA (ceRNA) regulation suggested complex network of all transcript RNAs including long noncoding RNAs (lncRNAs), which can act as natural miRNA sponges to inhibit miRNA functions and modulate mRNA expression. Until now, the specific ceRNA regulatory mechanism of lncRNA-miRNA-mRNA in colorectal cancer (CRC) still remains unclear.
Materials And Methods:
RNA sequencing data of 478 colon adenocarcinoma cases and 41 controls as well as 166 rectum adenocarcinoma cases and 10 controls were obtained from The Cancer Genome Atlas (TCGA) to investigate the significant changes of lncRNAs, miRNAs and mRNAs in colorectal carcinogenesis. The target lncRNAs and mRNAs of miRNAs were predicted by miRWalk. Functional and enrichment analyses were conducted by DAVID database. The lncRNA-miRNA-mRNA interaction network was constructed using Cytoscape.
Results:
We constructed ceRNA regulatory networks including 22 up-regulated lncRNAs, 12 down-regulated miRNAs and 122 up-regulated mRNAs, as well as 8 down-regulated lncRNAs, 43 up-regulated miRNAs and 139 down-regulated mRNAs. The GO enrichment showed that up-regulated genes mainly enriched in biological process including organic anion transport, collagen catabolic process, wound healing, Wnt receptor signalling and in pathways of tyrosine metabolism, taurine and hypotaurine metabolism, melanogenesis and phenylalanine metabolism. For down-regulated genes, significant enrichment was found in biological process of metal ion homeostasis, transmission of nerve impulse, cell-cell signalling, transmembrane transport and in pathways of ABC transporters, neuroactive ligand-receptor interaction, retinol metabolism, nitrogen metabolism and steroid hormone biosynthesis.
Conclusion:
We identified significantly altered lncRNAs, miRNAs and mRNAs in colorectal carcinogenesis, which might serve as potential biomarkers for tumorigenesis of CRC. In addition, the ceRNA regulatory network of lncRNA-miRNA-mRNA was constructed, which would elucidate novel molecular mechanisms involved in initiation and progression of CRC, thus providing promising clues for clinical diagnosis and therapy.
Insights
This study reveals altered long noncoding RNAs, microRNAs, and messenger RNAs in colorectal cancer (CRC), constructing a competitive endogenous RNA (ceRNA) network. These findings offer potential biomarkers and novel molecular insights for CRC diagnosis and therapy.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Competitive endogenous RNA (ceRNA) regulation involves complex interactions between long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs).
- lncRNAs can act as miRNA sponges, inhibiting miRNA function and influencing mRNA expression.
- The specific ceRNA regulatory mechanisms in colorectal cancer (CRC) remain largely unelucidated.
Purpose of the Study:
- To investigate significant changes in lncRNAs, miRNAs, and mRNAs during colorectal carcinogenesis.
- To construct the lncRNA-miRNA-mRNA ceRNA regulatory network in CRC.
- To identify potential biomarkers and molecular mechanisms underlying CRC initiation and progression.
Main Methods:
- Utilized RNA sequencing data from The Cancer Genome Atlas (TCGA) for colon and rectum adenocarcinoma.
- Predicted lncRNA-miRNA and miRNA-mRNA interactions using miRWalk.
- Performed functional and enrichment analyses with DAVID and constructed the ceRNA network using Cytoscape.
Main Results:
- Constructed ceRNA networks with altered lncRNAs, miRNAs, and mRNAs in CRC.
- Identified distinct enrichment pathways for up-regulated and down-regulated genes, including Wnt signaling, metabolism, and cell communication.
- Revealed significant alterations in lncRNAs, miRNAs, and mRNAs associated with colorectal carcinogenesis.
Conclusions:
- Significantly altered lncRNAs, miRNAs, and mRNAs in CRC may serve as potential biomarkers.
- The constructed ceRNA network elucidates novel molecular mechanisms in CRC initiation and progression.
- These findings provide promising insights for clinical diagnosis and therapeutic strategies for CRC.
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