Systematic analysis of lncRNA–miRNA–mRNA competing endogenous RNA network identifies four-lncRNA signature as a prognostic biomarker for breast cancer

Abstract

BackgroundIncreasing evidence has underscored the role of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in the development and progression of tumors. Nevertheless, lncRNA biomarkers in lncRNA-related ceRNA network that can predict the prognosis of breast cancer (BC) are still lacking. The aim of our study was to identify potential lncRNA signatures capable of predicting overall survival (OS) of BC patients.MethodsThe RNA sequencing data and clinical characteristics of BC patients were obtained from the Cancer Genome Atlas database, and differentially expressed lncRNA (DElncRNAs), DEmRNAs, and DEmiRNAs were then identified between BC and normal breast tissue samples. Subsequently, the lncRNA–miRNA–mRNA ceRNA network of BC was established, and the gene oncology enrichment analyses for the DEmRNAs interacting with lncRNAs in the ceRNA network was implemented. Using univariate and multivariate Cox regression analyses, a four-lncRNA signature was developed and used for predicting the survival in BC patients. We applied receiver operating characteristic analysis to assess the performance of our model.ResultsA total of 1061 DElncRNAs, 2150 DEmRNAs, and 82 DEmiRNAs were identified between BC and normal breast tissue samples. A lncRNA–miRNA–mRNA ceRNA network of BC was established, which comprised of 8 DEmiRNAs, 48 DElncRNAs, and 10 DEmRNAs. Further gene oncology enrichment analyses revealed that the DEmRNAs interacting with lncRNAs in the ceRNA network participated in cell leading edge, protease binding, alpha-catenin binding, gamma-catenin binding, and adenylate cyclase binding. A univariate regression analysis of the DElncRNAs revealed 7 lncRNAs (ADAMTS9-AS1, AC061992.1, LINC00536, HOTAIR, AL391421.1, TLR8-AS1 and LINC00491) that were associated with OS of BC patients. A multivariate Cox regression analysis demonstrated that 4 of those lncRNAs (ADAMTS9-AS1, LINC00536, AL391421.1 and LINC00491) had significant prognostic value, and their cumulative risk score indicated that this 4-lncRNA signature independently predicted OS in BC patients. Furthermore, the area under the curve of the 4-lncRNA signature associated with 3-year survival was 0.696.ConclusionsThe current study provides novel insights into the lncRNA-related ceRNA network in BC and the 4 lncRNA biomarkers may be independent prognostic signatures in predicting the survival of BC patients.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1640-2) contains supplementary material, which is available to authorized users.

Data Mining and Expression Analysis of Differential lncRNA ADAMTS9-AS1 in Prostate Cancer

“…Thus, it provides clinicians and patients with independent, clinically useful information to make more informed decisions regarding the need for biopsies. Additionally, we were also surprised to find that ADAMTS9-AS1 acts as a ceRNA that regulates the occurrence and development of tumors in breast cancer (Fan et al, 2018), bladder cancer , and colon adenocarcinoma (Xing et al, 2018).…”

Identification of lncRNA–miRNA–mRNA regulatory network associated with primary open angle glaucoma

“…The newly emerged ceRNA hypothesis has been suggested as an innovative post-transcriptional regulatory mechanism of gene expression. Under this ceRNA network, the lncRNAs and mRNAs are connected by their common target miRNAs [30]. In recent years, several studies have explored the underlying molecular mechanisms based on the ceRNA network in some diseases, such as breast cancer [31], ischemic stroke [32], and rheumatoid arthritis [33].…”

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

“…Under this ceRNA network, the lncRNAs and mRNAs are connected by their common target miRNAs [30]. In recent years, several studies have explored the underlying molecular mechanisms based on the ceRNA network in some diseases, such as breast cancer [32], ischemic stroke [33], and rheumatoid arthritis [34]. To identify lncRNAs significantly associated with POAG, in this study, the mRNA and lncRNA expression profiles of POAG patients were first used and combined with miRNA-target interactions to create a ceRNA network and to investigate the potential implications of these lncRNAs in the development of POAG.…”