Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma

Zhiyuan Zhang; Wenwei Qian; Sen Wang; Dongjian Ji; Qingyuan Wang; Jie Li; Wen Peng; Jiou Gu; Tao Hu; Bing Ji; Yue Zhang; Shijia Wang; Yueming Sun

doi:10.1159/000493623

Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma

Cell Physiol Biochem. 2018;49(5):1778-1791. doi: 10.1159/000493623. Epub 2018 Sep 19.

Authors

Zhiyuan Zhang^{1

2}, Wenwei Qian^{1

2}, Sen Wang^{1

2}, Dongjian Ji^{1

2}, Qingyuan Wang^{1

2}, Jie Li^{1

2}, Wen Peng^{1

2}, Jiou Gu^{1

2}, Tao Hu^{1

2}, Bing Ji^{1

2}, Yue Zhang^{1

2}, Shijia Wang^{1

2}, Yueming Sun²

Affiliations

¹ The First School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
² Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

PMID: 30231249
DOI: 10.1159/000493623

Abstract

Background/aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD.

Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR).

Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log2 [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR.

Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.

Keywords: Bioinformatics analysis; Biomarkers; Colon adenocarcinoma; LncRNA; ceRNA network.

MeSH terms

Adenocarcinoma / genetics
Adenocarcinoma / mortality
Adenocarcinoma / pathology*
Aged
Aged, 80 and over
Biomarkers, Tumor / genetics*
Colonic Neoplasms / genetics
Colonic Neoplasms / mortality
Colonic Neoplasms / pathology*
Female
Gene Regulatory Networks / genetics*
Humans
Kaplan-Meier Estimate
Male
MicroRNAs / metabolism
Middle Aged
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
RNA, Messenger / metabolism

Substances

Biomarkers, Tumor
MicroRNAs
RNA, Long Noncoding
RNA, Messenger