Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer.
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.
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
Wenting
W
Wu
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
Erin K
EK
Wagner
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Yangyang
Y
Hao
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Xi
X
Rao
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, National Clinical Research Center for Cancer, Tianjin &Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Hongji
H
Dai
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Jiali
J
Han
Spinal Cord and Brain Injury Research Group, Department of Neurosurgery, Stark Neuroscience Research Institute, Indiana University, Indianapolis, IN, USA.
Jinhui
J
Chen
Susan G. Komen Tissue Bank at the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Anna Maria V
AMV
Storniolo
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.|Center for Computational Biology and Bioinformatics, Indiana University, Indianapolis, IN 46202, USA.
Yunlong
Y
Liu
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.|Center for Computational Biology and Bioinformatics, Indiana University, Indianapolis, IN 46202, USA.
Chunyan
C
He
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D062085:RNA, Long Noncoding; D012333:RNA, Messenger