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
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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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DOI: https://doi.org/10.1007/s10142-017-0588-2