Comprehensive analysis of the aberrantly expressed IncRNA-associated ceRNA network in breast cancer

Abstract

Previous studies have suggested that long non-coding RNAs (lncRNAs) are closely associated with human diseases, particularly cancer, including cancer of the lung, breast and stomach. A variety of lncRNAs are abnormally expressed in cancer and participate in several pathways including cell proliferation and apoptosis; these elements are closely associated with the development of cancer. The cancer Genome Atlas (TcGA) is an important cancer database. It consists of clinical data, genomic variation, mRNA, microRNA (miRNA) and lncRNAs expression, methylation and other data for various types of human cancer. In the present study, differential expression of RNA was identified using the edgeR package. A total 1,222 RNA sequencing profiles from patients with breast cancer were downloaded from TcGA. A competing endoge¬ nous RNA (ceRNA) network was constructed for breast cancer based on miRcode and miRTarBase. The top 10 lncRNAs were selected using cox regression analysis. Survival analysis was performed using Kaplan-Meier analysis. A total of 1,028 breast cancer-associated lncRNAs and 89 mimas (fold change >2; P<0.05) were identified; among these, 93 lncRNAs and 19 miRNAs were included in the ceRNA network. Subsequently, 10 basic lncRNAs were selected and their associations with overall survival were identified. In addition, 5 lncRNAs (A D A M metallopeptidase with thrombospondin type 1 motif 9-antisense RNA 1, AL513123.1, chromosome 10 open reading frame 126, long intergenic non-protein coding RNA 536 and Wilms tumor 1 antisense RNA) were identified to be significantly associated with overall survival (P<0.05, log rank test). These results suggested that mRNAs, lncRNAs and miRNAs were involved in pathological mecha¬ nisms of breast cancer. The newly-identified ceRNA network included 93 breast cancer-specific lncRNAs, 19 miRNAs and 27 HIRNAS. The results of the present study highlight the potential of lncRNAs in understanding the development and pathogenesis of breast cancer, and suggest novel concepts and an experimental basis for the identification of prognostic biomarkers and therapeutic targets for breast cancer.