So alike yet so different. Differential expression of the long non-coding RNAs NORAD and HCG11 in breast cancer subtypes

Breast cancer (BC) is a heterogeneous disease, and it is the leading cause of death among women. NORAD and HCG11 are highly similar lncRNAs that present binding sites for PUMILIO proteins. PUMILIO acts on hundreds of mRNA targets, contributing to the modulation of gene expression. We analyzed the expression levels of NORAD and HCG11 in the BC subtypes luminal A (LA) and basal-like (BL), and the regulatory networks associated with these lncRNAs. In the analysis of TCGA cohort (n=329) and Brazilian BC samples (n=44), NORAD was up-regulated in LA while HCG11 was up-regulated in BL subtype. An increased expression of NORAD is associated with reduced disease-free survival in basal-like patients (p = 0.002), which suggests that its prognostic value could be different in specific subtypes. The biological pathways observed for the HCG11 network are linked to the epithelial-to-mesenchymal transition; while NORAD associated pathways appear to be related to luminal epithelial cell transformation. NORAD and HCG11 regulons respectively present 36% and 21.5% of PUMILIO targets, which suggests that these lncRNAs act as a decoy for PUMILIO. These lncRNAs seem to work as players in the differentiation process that drives breast cells to acquire distinct phenotypes related to a specific BC subtype.