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.

中文翻译：

---

如此相似又如此不同。长非编码 RNA NORAD 和 HCG11 在乳腺癌亚型中的差异表达。


乳腺癌（BC）是一种异质性疾病，是女性死亡的主要原因。 NORAD 和 HCG11 是高度相似的 lncRNA，它们呈现 PUMILIO 蛋白的结合位点。 PUMILIO 作用于数百个 mRNA 靶点，有助于基因表达的调节。我们分析了 BC 亚型 luminal A (LA) 和 basal-like (BL) 中 NORAD 和 HCG11 的表达水平，以及与这些 lncRNA 相关的调控网络。在 TCGA 队列 (n=329) 和巴西 BC 样本 (n=44) 的分析中，NORAD 在 LA 亚型中上调，而 HCG11 在 BL 亚型中上调。 NORAD 表达增加与基础样患者无病生存率降低相关 (p = 0.002)，这表明其预后价值在特定亚型中可能不同。观察到的 HCG11 网络的生物学途径与上皮间质转化有关；而 NORAD 相关途径似乎与管腔上皮细胞转化有关。 NORAD 和 HCG11 调节子分别占 PUMILIO 靶点的 36% 和 21.5%，这表明这些 lncRNA 充当 PUMILIO 的诱饵。这些 lncRNA 似乎在分化过程中发挥作用，驱动乳腺细胞获得与特定 BC 亚型相关的独特表型。