Analysis of the miRNA-mRNA-lncRNA network in human estrogen receptor-positive and estrogen receptor-negative breast cancer based on TCGA data.

Abstract Estrogen receptor-positive (ER + ) and ER-negative (ER − ) subtypes of breast cancer have distinct clinical outcomes because they respond differentially to endocrine therapies. We aimed to comprehensively analyze differentially expressed microRNA (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs in different ER subtypes as well as to identify prognosis-related RNAs. The expression levels of miRNAs, lncRNAs, and mRNAs between breast cancer and normal samples were compared using data from The Cancer Genome Atlas database. Differentially expressed miRNAs, lncRNAs and mRNAs between ER + and ER − samples were also screened. An ER subtype-related miRNA–lncRNA–mRNA network was constructed. lncRNAs and mRNAs in this network were further subjected to an analysis of their associations with patient prognosis. Sets of differentially expressed miRNAs, lncRNAs, and miRNAs between breast cancer and normal samples were identified among which 14 miRNAs, 78 lncRNAs, and 475 mRNAs were differentially expressed between ER subtypes. Relationships between these RNAs were analyzed. The resultant ER subtype-related miRNA–lncRNA–mRNA network consisted of 14 nodes, among which LINC0092 and chromosome 2 open reading frame 71 (C2orf71) were correlated with better prognosis of breast cancer. LINC0092 was co-expressed with SFRP1 and RGMA and regulated by hsa-miR-449a and hsa-miR-452–5p. C2orf71 was co-expressed with LINC00511 and regulated by hsa-miR-184. Cross-talk among differentially expressed miRNAs, lncRNAs, and miRNAs may be an important feature in ER + and ER − subtypes of breast cancer. LINC0092 and C2orf71, two of these cross-talking RNAs, may serve as novel prognostic predictor of breast cancer because of their close associations with prognosis.