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Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA–miRNA–mRNA in Colorectal Carcinogenesis

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Abstract

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.

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Funding

This study is supported by grants from Public Welfare Foundation of Liaoning Province (No. 2015005002).

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Authors and Affiliations

  1. Tumor 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

    Jingwei Liu, Hao Li, Bowen Zheng, Liping Sun, Yuan Yuan & Chengzhong Xing

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  1. Jingwei Liu
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  2. Hao Li
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  3. Bowen Zheng
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Correspondence to Yuan Yuan or Chengzhong Xing.

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Liu, J., Li, H., Zheng, B. et al. Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA–miRNA–mRNA in Colorectal Carcinogenesis. Dig Dis Sci 64, 1868–1877 (2019). https://doi.org/10.1007/s10620-019-05506-9

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  • DOI: https://doi.org/10.1007/s10620-019-05506-9

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