Comprehensive analysis of long non-coding RNAs in human breast cancer clinical subtypes

Abstract

Accumulating evidence highlights the potential role of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in solid tumors. However, the role of lncRNA expression in human breast cancer biology, prognosis and molecular classification remains unknown. Herein, we established the lncRNA profile of 658 infiltrating ductal carcinomas of the breast from The Cancer Genome Atlas project. We found lncRNA expression to correlate with the gene expression and chromatin landscape of human mammary epithelial cells (non-transformed) and the breast cancer cell line MCF-7. Unsupervised consensus clustering of lncRNA revealed four subgroups that displayed different prognoses. Gene set enrichment analysis for cis- and trans-acting lncRNAs showed enrichment for breast cancer signatures driven by master regulators of breast carcinogenesis. Interestingly, the lncRNA HOTAIR was significantly overexpressed in the HER2-enriched subgroup, while the lncRNA HOTAIRM1 was significantly overexpressed in the basal-like subgroup. Estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Importantly, almost two thirds of the lncRNAs were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that expressed lncRNA in breast cancer drives carcinogenesis through increased activity of neighboring genes. In summary, our study depicts the first lncRNA subtype classification in breast cancer and provides the framework for future studies to assess the interplay between lncRNAs and the breast cancer epigenome.

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

“…HOTAIRM1 may affect cell fate by regulating cell cycle progression and serving as a link in the coordinated regulation of an extensive gene expression program. Although, the expression of HOTAIRM1 was previously shown to be specific to the myeloid lineage of hematopoietic cells (72), a recent study reported that the HOTAIRM1 was overexpressed in the basal-like subtype of breast cancer (73). Together with our present study in PDAC tissues by microarray and qRT-PCR, the long intergenic noncoding RNA HOTAIRM1 may participate in the development and progression of several cancers.…”

Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value

“…Furthermore, lncRNAs are potential therapeutic targets, and inhibition or overexpression of tumor-specific lncRNAs might have therapeutic implications in TNBC patients (24,25). Recent studies identified several lncRNAs in tight connection with breast cancer (26,27). Su and colleagues (26) divided breast cancer into four different subtypes using lncRNAs data from The Cancer Genome Atlas (TCGA) database and revealed a cluster that was highly correlated with basal-like breast cancer.…”

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…A recent review of the function of selected lncRNAs upregulated (19) and downregulated (5) (Su et al 2014). HOTAIRM1 SOX9 is a stem cell factor involved in tamoxifen resistant BCa (Jeselsohn, et al 2017).…”