The regulatory network analysis of long noncoding RNAs in human colorectal cancer

Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

doi:10.1007/s10142-017-0588-2

Original Article
Published: 26 January 2018

The regulatory network analysis of long noncoding RNAs in human colorectal cancer

Yuwei Zhang¹,
Yang Tao¹,
Yang Li²,
Jinshun Zhao¹,
Lina Zhang¹,
Xiaohong Zhang¹,
Changzheng Dong¹,
Yangyang Xie³,
Xiaoyu Dai³,
Xinjun Zhang⁴ &
Qi Liao¹

Functional & Integrative Genomics volume 18, pages 261–275 (2018)Cite this article

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Abstract

Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

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Acknowledgements

Natural Science Foundation of Ningbo (no. 2017A610154 and no. 2016A610121, no. 2017A610145, no. 2017A610158, no. 2016A610135), the National Natural Science Foundation of China (no. 31301084), the Zhejiang Provincial Natural Science Foundation of China (no. LQ13C060002), the Scientific Innovation Team Project of Ningbo (no. 2016C51001), the Medical and Health Science and Technology Foundation of Zhejiang Province (no. 2017KY593, no. 2018KY690, no. 2018KY699, no. 2017KY594), and the K.C. Wong Magna Fund at Ningbo University

Author information

Yuwei Zhang and Yang Tao have equal contributions to the work.

Affiliations

Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo, Zhejiang, 315211, China
Yuwei Zhang, Yang Tao, Jinshun Zhao, Lina Zhang, Xiaohong Zhang, Changzheng Dong & Qi Liao
Faulty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China
Yang Li
Anorectal Surgery, Ningbo Second Hospital, Ningbo, 315000, China
Yangyang Xie & Xiaoyu Dai
The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, 315020, China
Xinjun Zhang

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Yuwei Zhang
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Yang Tao
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Yang Li
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Jinshun Zhao
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Lina Zhang
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Xiaohong Zhang
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Changzheng Dong
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Yangyang Xie
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Xiaoyu Dai
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Xinjun Zhang
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Qi Liao
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Correspondence to Qi Liao.

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Electronic supplementary material

Supplementary File 1

The list of lncRNA-TF interactions. The first column in this list is lncRNAs, and the second column is the target TFs. (TXT 18kb)

Supplementary File 2

The list of lncRNA-TF interactions with cell line specificity in the colon. (TXT 2kb)

Supplementary File 3

The list of lncRNA-miRNA interactions. The first column in this list is lncRNAs, and the second column is the target miRNAs. (TXT 143kb)

Supplementary File 4

The list of the ceRNA relationships. The first column in this list is lncRNAs, and the second column is the competing mRNAs. (TXT 38kb)

Supplementary File 5

The list of lncRNA-RBP interactions. The first column in this list is lncRNAs, and the second column is the target RBPs. (TXT 40kb)

Supplementary File 6

The list of the up-regulated genes in CRC regulatory network. (TXT 6kb)

Supplementary File 7

The list of the down-regulated genes in CRC regulatory network. (TXT 7kb)

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Zhang, Y., Tao, Y., Li, Y. et al. The regulatory network analysis of long noncoding RNAs in human colorectal cancer. Funct Integr Genomics 18, 261–275 (2018). https://doi.org/10.1007/s10142-017-0588-2

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Received: 11 August 2017
Revised: 22 December 2017
Accepted: 29 December 2017
Published: 26 January 2018
Issue Date: May 2018
DOI: https://doi.org/10.1007/s10142-017-0588-2

Keywords

Colorectal cancer
Long noncoding RNA
Regulatory network
Functional annotation
Bioinformatics approaches