Abstract

Abstract Interactions between long non-coding RNAs (lncRNAs) and proteins contribute to the epigenetic regulation of gene expression, and defects in such interactions have been implicated in several diseases, including cancer. Basal-like breast cancer accounts for approximately 15% of all breast cancer and is a major clinical problem given its poor survival and lack of responsiveness to targeted breast cancer treatments. DNA methylation is non-random and is much more pronounced in basal-like breast cancer (BLBC) compared to other molecular subtypes of breast cancer, raising the possibility that hypermethylation could be important in the genesis of BLBCs. LncRNAs are aberrantly expressed in multiple subtypes of breast cancer, including BLBC, and are considered to have significant prognostic potential. In order to explore the potential roles of DNA methylation and lncRNAs in BLBC, we investigated lncRNA-protein interactions using bioinformatics and molecular techniques, focusing on proteins that actively perform DNA methylation - the DNA methyltransferase (DNMT) family. Our novel bioinformatic methods revealed that BLBC may be sub-classified according to methylation profile in a way that could predict disease survival. We then identified candidate lncRNAs that are over-expressed in BLBC and statistically predicted to interact with DNMT proteins. Using RNA immunoprecipitation of BLBC cell lines, we have identified potential lncRNA-protein interactions that may be involved in epigenetic remodelling in BLBC. The role of these lncRNAs in epigenetic gene regulation and BLBC is currently being explored. Citation Format: Northwood K, Saunus J, Milevskiy M, Lakhani S, Brown M. RNA immunoprecipitation reveals lncRNA-protein interactions in basal-like breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-04-05.

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