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.
Highlights
Breast cancer is a genetically malignant tumor caused by a variety of elements involving the accumulation of genetic changes [1,2,3]
The first category of long non-coding RNAs (lncRNAs) were the high methylated lncRNAs (HMLncs) that DNA methylation level in promoter was up-regulated compared with normal samples
The other category of lncRNAs were the low methylated lncRNAs (LMLncs) that DNA methylation level in promoter was downregulated compared with normal samples
Summary
Breast cancer is a genetically malignant tumor caused by a variety of elements involving the accumulation of genetic changes [1,2,3]. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are crucial directions in the researches of ncRNAs. The miRNAs inhibit the translation or regulation of target genes that carry miRNA binding sites in their 3ʹ untranslated regions (UTRs) [6]. The miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 regulated epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [9]. These two genes were involved in epithelial to mesenchymal transition and tumor metastasis. For lncRNAs, Jadaliha et al [11] used MALAT1 knockdown/ overexpression experiments to confirm the functional significance of MALAT1 as a metastasis driver and a prognostic factor in ER negative, lymph node negative breast cancer. NcRNAs have been www.impactjournals.com/oncotarget described with relatively definite molecular mechanisms in cancers, the regulatory mechanisms of ncRNAs in tumors were unclear especially DNA methylation of lncRNAs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
