Abstract
Abstract Long non-coding RNA (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 lncRNAs in the transcription field is beginning to be explored and their roles have been found to vary from guiding proteins to the genome to scaffolding proteins complexes needed for the transcription of a specific gene. 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 the samples, originally analyzed by microarray, to understand the role of lncRNAs in the regulation of transcription and their potential function in pregnancy's preventive 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, 11 lncRNAs were selected to be tested in vitro. Using RT-qPCR we have determined that the expression of these 11 lncRNAs is characteristic of each epithelial breast cancer cell subtype (luminal, basal and cells that overexpress HER2). These results indicate that these lncRNAs may be key targets to specifically study and potentially treat different types of breast cancers. Moreover, these lncRNAs are differentially expressed when breast tumor tissue and its adjacent normal tissue are compared. Consequently, the results in cancer/normal-like cell lines and tumor/adjacent normal 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 provides novel information on lncRNAs differentially expressed in breast cells when comparing pregnancy versus the lack of a full term pregnancy, and also places lncRNAs as potential key regulators in cancer initiation and cancer progression. Determining their functions in both differentiation and cancer will render a comprehensive picture of their role in the human breast at the transcriptomic level. Furthermore, the manipulation of these lncRNAs can eventually lead to the development of therapeutics for breast cancer prevention. (This work was supported by NIH core grant CA06927 to Fox Chase Cancer Center) Citation Format: Maria Barton, Julia Santucci-Pereira, Theresa D. Nguyen, Jose Russo. Long noncoding RNAs in the breast of healthy women are detected in different subtypes of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 164. doi:10.1158/1538-7445.AM2015-164
Published Version
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