lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Construction and Comprehensive Analysis of a Competitive Endogenous RNA Network and Potential Regulatory Axes in Gastric Cancer

22 Pages Posted: 12 Apr 2019

See all articles by Hongda Pan

Hongda Pan

Fudan University - Department of Gastric Surgery

Jingxin Pan

Fujian Medical University

Dongwei Guo

Sun Yat-Sen University (SYSU) - State Key Laboratory of Ophthalmology

Shibo Song

Government of the People's Republic of China, Ministry of Health, Beijing Hospital

Yibin Guo

Sun Yat-Sen University (SYSU)

Dazhi Xu

Fudan University - Department of Gastric Surgery

More...

Abstract

Background: Long non-coding RNAs (lncRNAs) have been identified as micro RNA (miRNA) sponges in a competing endogenous RNA (ceRNA) network, and are involved in the regulation of gene expression. This study aims to construct a lncRNA-associated ceRNA network in GC.

Methods: Differentially expressed lncRNAs, mRNAs, and miRNAs were identified by analyzing the expression profiles of GC retrieved from The Cancer Genome Atlas (TCGA) database. The lncRNA-miRNA-mRNA regulatory networks of GC were constructed by comprehensive bioinformatics methods including functional annotation, RNA-RNA interactomes prediction, correlation analysis, and survival analysis. The interactions and correlations among ceRNAs were validated by experiments on cancer tissues and cell lines.

Results: A total of 41 lncRNAs, 9 miRNAs, and 10 mRNAs were identified and selected to establish the ceRNA regulatory network of GC. Several ceRNA regulatory axes, which consist of 18 lncRNAs, 4 miRNAs, and 6 mRNAs, were obtained from the network. A potential ADAMTS9-AS2/miR-372/CADM2 axis which perfectly conformed to the ceRNA theory was further analyzed. qRT-PCR revealed that ADAMTS9-AS2 knockdown significantly increased miR-372 expression but reduced CADM2 expression, while ADAMTS9-AS2 overexpression had the opposite effects. Dual luciferase reporter assay indicated that miR-372 could bound to the ADAMTS9-AS2 and the 3'UTR of CADM2.

Conclusions: The constructed novel ceRNA network and the potential regulatory axes might provide a comprehensive understanding of the potential mechanisms of development in GC. The ADAMTS9-AS2/miR-372/CADM2 axis could serve as a potential therapeutic target for GC treatment.

Funding Statement: This study was supported by Beijing Natural Science Foundation (7184240).

Declaration of Interests: The authors declare: "None."

Ethics Approval Statement: Written informed consent was obtained from all patients. This study was performed with the approval of the Ethics Committee of the Beijing Hospital.

Keywords: Gastric cancer; Competing endogenous RNA; Bioinformatics analysis; Prognostic biomarker; Experimental validation

Suggested Citation

Pan, Hongda and Pan, Jingxin and Guo, Dongwei and Song, Shibo and Guo, Yibin and Xu, Dazhi, Construction and Comprehensive Analysis of a Competitive Endogenous RNA Network and Potential Regulatory Axes in Gastric Cancer (September 4, 2019). Available at SSRN: https://ssrn.com/abstract=3369753

Hongda Pan

Fudan University - Department of Gastric Surgery

China

Jingxin Pan

Fujian Medical University

Fuzhou
China

Dongwei Guo

Sun Yat-Sen University (SYSU) - State Key Laboratory of Ophthalmology

54# Xianlie S. Road
Guangzhou, 510060
China

Shibo Song

Government of the People's Republic of China, Ministry of Health, Beijing Hospital

China

Yibin Guo

Sun Yat-Sen University (SYSU) ( email )

135, Xingang Xi Road
Guangzhou, Guangdong 510275
China

Dazhi Xu (Contact Author)

Fudan University - Department of Gastric Surgery ( email )

China

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
55
Downloads
21