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.
|State||Published - Sep 6 2016|
Bibliographical noteFunding Information:
This research was supported by NIH R01 grant R01CA194030 from the National Cancer Institute and Career Catalyst Research grant CCR15333233 from Susan G. Komen. CH is supported by Indiana University Simon Cancer Center Breast Cancer Program and Cancer Prevention and Control Program. We acknowledge Indiana CTSI Specimen Storage Facility (SSF), which is supported by NCRR Clinical and Translational Sciences Award (U54-RR025761) and NCRR construction award (C06-RR020128-01).
© The Author(s) 2016.
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