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

Abstract

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 diseasefree 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.

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

“…NORAD stimulated TGF-β signaling and directly increased RUNX2 expression, resulting in BC progression and metastasis [ 228 ]. The NORAD level was higher in luminal A tumors compared to basal-like or TNBC breast tumors [ 229 ]. High expression of NORAD in basal-like cancers was associated with lower OS; however, NORAD offered no prognostic information in luminal A BC tumors [ 229 ].…”

“…The NORAD level was higher in luminal A tumors compared to basal-like or TNBC breast tumors [ 229 ]. High expression of NORAD in basal-like cancers was associated with lower OS; however, NORAD offered no prognostic information in luminal A BC tumors [ 229 ].…”

High RRM2 expression has poor prognosis in specific types of breast cancer

“…Mathias C et al found that in different subtypes of breast cancer, differentially expressed genes can affect the OS of breast cancer patients [ 30 – 33 ]. To determine whether the high expression of RRM2 was associated with the molecular subtypes of breast cancer, we conducted KM survival analysis.…”

The Role of lncRNA in the Development of Tumors, including Breast Cancer

“…PUMILIO acts on hundreds of target mRNAs, helping to modulate gene expression. Mathias et al analyzed NORAD and HCG11 expression levels in luminal A and basal-like breast cancer subtypes and the regulatory networks associated with these lncRNAs [48]. NORAD was upregulated in luminal A, while HCG11 was upregulated in the basal-like subtype.…”