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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Colorectal Cancer | Primary research

LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network

Authors: Min-Er Zhong, Yanyu Chen, Guannan Zhang, Lai Xu, Wei Ge, Bin Wu

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of long non-coding RNA H19 in colorectal cancer.

Methods

Large-scale RNA-seq data was obtained from The Cancer Genome Atlas database. Differentially expressed RNAs were identified by bioinformatics analysis, and a competing endogenous RNA network was constructed. Functional enrichment analysis and correlation analysis between competing endogenous RNAs and clinical features were performed to reveal their roles in the tumorigenesis of colorectal cancer. To verify the conclusions derived from bioinformatics analysis, we investigated the effect of lncRNA H19 knockdown in human colorectal cancer cell lines HT-29 and HCT116.

Results

The present study successfully identify various cancer-specific lncRNAs and pseudogenes in CRC. The lncRNA/pseudogene–miRNA–mRNA ceRNA network was constructed using 10 lncRNAs, 5 pseudogenes, 122 mRNAs and 39 miRNAs. In the ceRNA network of CRC, H19 up-regulates various cancer-related mRNA by competitively sponging various miRNA, and participates in PI3K–Akt signaling pathway in this manner. Cox regression and correlation analysis showed that H19 and some other competing endogenous RNAs in the network are associated with poor prognosis and clinical parameters such as tumor grade and metastasis. Knockdown of H19 reduces the protein level of MET, ZEB1, and COL1A1 in vitro.

Conclusions

H19 regulates PI3K–Akt signal pathway through a competing endogenous RNA network and predicts poor prognosis in colorectal cancer. The pseudogene RPLP0P2 may be an important oncogene like H19 and needs to be studied further.
Appendix
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Metadata
Title
LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
Authors
Min-Er Zhong
Yanyu Chen
Guannan Zhang
Lai Xu
Wei Ge
Bin Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0866-2

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