Abstract P6-04-08: Expression profile of long non-coding RNAs characterizes different subtypes of breast cancer

Abstract

Abstract Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are not translated into proteins, but regulate the transcription of genes involved in different cellular processes, including differentiation, cancer initiation and progression. The relevance of several lncRNAs in the transcriptional and post-transcriptional field is now well established. Their roles have been found to vary from forming complexes needed for gene transcription to having critical roles in the cytoplasm where they regulate protein localization, mRNA translation and stability. Microarray analysis of normal breast of parous and nulliparous postmenopausal women revealed that lncRNAs are up-regulated in the parous breast [Int. J. Cancer: 131, 1059-1070, 2012]. Subsequently, RNA sequencing was performed to a subset of these samples to understand the role of lncRNAs in the regulation of transcription and their potential function in pregnancy's effect in reducing the lifetime risk of developing breast cancer. In this work, RNA sequencing of healthy postmenopausal breast tissue biopsies from 8 parous and 8 nulliparous women using Illumina platform was performed. The sequencing results show that there are 42 lncRNAs differentially expressed between parous and nulliparous breast tissue. After analysis of these 42 lncRNAs using bioinformatics and thermodynamic filters, 10 lncRNAs were selected to be tested in vitro. Using RT-qPCR, we have demonstrated that the expression profile of at least 10 lncRNAs is characteristic of each epithelial breast cancer cell subtype (luminal, triple negative and cells that overexpress HER2). Moreover, these lncRNAs are differentially expressed in breast tumors when compared to its adjacent normal tissue. Overexpression and knock out experiments of several of these lncRNAs are underway to prove their relevance in breast differentiation and cancer initiation. The results in cancer/normal immortalized breast cell lines and tumor/adjacent normal breast tissue point to the potential of these lncRNAs as targets, not only for therapeutic approaches against breast cancer, but also as preventive measures for nulliparous women. (This work was supported by NIH core grant CA06927 to Fox Chase Cancer Center). Citation Format: Barton M, Santucci-Pereira J, Russo J. Expression profile of long non-coding RNAs characterizes different subtypes of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-08.