Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer

Abstract

Inference of the biological roles of lncRNAs in breast cancer development remains a challenge. Here, we analyzed RNA-seq data in tumor and normal breast tissue samples from 18 breast cancer patients and 18 healthy controls and constructed a functional lncRNA-mRNA co-expression network. We revealed two distinctive co-expression patterns associated with breast cancer, reflecting different underlying regulatory mechanisms: (1) 516 pairs of lncRNA-mRNAs have differential co-expression pattern, in which the correlation between lncRNA and mRNA expression differs in tumor and normal breast tissue; (2) 291 pairs have dose-response co-expression pattern, in which the correlation is similar, but the expression level of lncRNA or mRNA differs in the two tissue types. We further validated our findings in TCGA dataset and annotated lncRNAs using TANRIC. One novel lncRNA, AC145110.1 on 8p12, was found differentially co-expressed with 127 mRNAs (including TOX4 and MAEL) in tumor and normal breast tissue and also highly correlated with breast cancer clinical outcomes. Functional enrichment and pathway analyses identified distinct biological functions for different patterns of co-expression regulations. Our data suggested that lncRNAs might be involved in breast tumorigenesis through the modulation of gene expression in multiple pathologic pathways.

Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma

“…While most of these pairs (2698, 91.2%) were on the different chromosome ( trans -acting), suggesting that most of the regulation of lncRNA and mRNA expression was in a trans way. These findings are also consistent with previous reports [ 23 , 24 ].…”

Integrated analysis of long noncoding RNA and mRNA expression profiles reveals the potential role of long noncoding RNA in different bovine lactation stages

“…This suggested that most of the lncRNA trans-regulate mRNA expression. Such regulation pattern was also observed in a human cancer-related study (Wu et al, 2016).…”

“…Functional studies in humans have used similar models. Wu et al (2016) used this method to identify lncRNA-mRNA coexpression pairs associated with breast cancer, and Guo et al (2015) investigated the expression patterns of lncRNA and mRNA in ovarian cancer malignant progression. Thus, using this model might help improve lncRNA annotation.…”

Dysregulated lncRNA-miRNA-mRNA Network Reveals Patient Survival-Associated Modules and RNA Binding Proteins in Invasive Breast Carcinoma

“…Li et al (2018a) found that some of the correlations between microRNA and target genes declined in cancer compared to normal across multiple cancers. Wu et al (2016a) found two kinds of lncRNA-mRNA co-expression patterns: 1) correlations between lncRNA-mRNA in cancer were reversed compared to normal; 2) correlations between lncRNA-mRNA in cancer were similar to normal. Xiao et al (2018) compared the differential genes between ER+ and ERand constructed a ceRNA network and found that some molecules correlated with prognosis.…”