The landscape of DNA methylation-mediated regulation of long non-coding RNAs in breast cancer

Abstract

Although systematic studies have identified a host of long non-coding RNAs (lncRNAs) which are involved in breast cancer, the knowledge about the methyla-tion-mediated dysregulation of those lncRNAs remains limited. Here, we integrated multi-omics data to analyze the methylated alteration of lncRNAs in breast invasive carcinoma (BRCA). We found that lncRNAs showed diverse methylation patterns on promoter regions in BRCA. LncRNAs were divided into two categories and four subcategories based on their promoter methylation patterns and expression levels be-tween tumor and normal samples. Through cis-regulatory analysis and gene ontology network, abnormally methylated lncRNAs were identified to be associated with can-cer regulation, proliferation or expression of transcription factors. Competing endog-enous RNA network and functional enrichment analysis of abnormally methylated lncRNAs showed that lncRNAs with different methylation patterns were involved in several hallmarks and KEGG pathways of cancers significantly. Finally, survival analysis based on mRNA modules in networks revealed that lncRNAs silenced by high methylation were associated with prognosis significantly in BRCA. This study enhances the understanding of aberrantly methylated patterns of lncRNAs and pro-vides a novel insight for identifying cancer biomarkers and potential therapeutic tar-gets in breast cancer.

Long non-coding RNA RAB11B-AS1 prevents osteosarcoma development and progression via its natural antisense transcript RAB11B

“…Recently, epigenetic silencing of tumor-suppressor lncRNA by aberrant DNA hyper-methylation attracts increasing attention in a variety of cancer [ 27 – 29 ]. To explore the epigenetic mechanism by which lnc- RAB11B-AS1 is regulated in osteosarcoma, we assessed the DNA methylation status of promoter region of lnc- RAB11B-AS1 in six paired osteosarcoma and adjacent normal samples.…”

MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches

“…Epigenetic modifications account for aberrant expression of short ncRNAs [ 30 ], but are also implicated in lncRNA dysregulation. Zhang and colleagues integrated multi-omics data to assess alterations of lncRNA methylation in breast invasive carcinoma, highlighting abnormally methylated lncRNAs involved in several hallmarks of cancers [ 31 ]. In multiple myeloma (MM) cells, the methylation of promoter-associated CpG islands triggered downregulation of KIAA0495, a lncRNA transcribed from chromosome 1p36 [ 32 ]; CpG island hypermethylation also downregulated the KIAA0495/p53-dependent apoptotic modulator PDAM, which in turn established a drug resistant phenotype in glioma cells [ 33 ].…”

LINC00261 Is an Epigenetically Regulated Tumor Suppressor Essential for Activation of the DNA Damage Response

“…Large-scale profiling studies, such as that performed by The Cancer Genome Atlas (TCGA), have revealed thousands of differentially expressed lncRNAs in multiple cancers (12,18), yet little is known of how these candidates function at a molecular level to regulate cellular phenotypes (19). In addition, epigenetic alterations to lncRNA expression have been suggested to contribute to the cancer phenotype (20,21). Only a few lncRNAs have been implicated in LUAD development (22)(23)(24)(25), including H19, ANRIL, MEG3, NEAT1, and MALAT1 (25).…”