Crosstalk among abnormal pathways widely occurs in human
cancer and generally leads to insensitivity to
cancer treatment. How long non-coding RNAs (lncRNAs) participate in the regulation of an abnormal pathway crosstalk in human
cancer is largely unknown. Here, we proposed a strategy that integrates
mRNA and
lncRNA expression profiles for systematic identification of
lncRNA-mediated crosstalk among risk pathways in different
breast cancer subtypes. We identified 12 to 44 crosstalking pathway pairs mediated by 28 to 49 lncRNAs in four
breast cancer subtypes. An
LncRNA-mediated crosstalking pathway network in each
breast cancer subtype was then constructed. We observed a number of
breast cancer subtype-specific crosstalks of risk pathways. These subtype-specific
lncRNA-mediated pathway crosstalks largely determined subtype-selective functions. Notably, we observed that lncRNAs mediated the crosstalk of pathways by cooperating with known important
protein-coding genes, which play core roles in the deterioration of
breast cancer. And we also identified key lncRNAs contributing to the crosstalk network in each subtype. As an example, the low expression of LIFR-AS1 was associated with poor survival in LumB subtype, and its cooperated genes IL1R and TGFBR located at the most upstream of the MAPK signaling pathway shared a common cascade path (p38 MAPKs-MEF2C) that can result in proliferation, differentiation and apoptosis. In summary, we offer an effective way to characterize complex crosstalks mediated by lncRNAs in
breast cancer subtypes, which can be applied to other diseases and provide useful information for understanding the pathogenesis of human
cancer.