Abstract 3555: LncRNA-21a is a potential tumor suppressor in breast cancer

Abstract

Abstract Long non-coding RNA (lncRNA)-21A is a polymerase III driven non-coding RNA consisting of 324 nucleotides in length. LncRNA-21A was originally identified through in silico analysis and its expression was then confirmed in human cell lines. Further study suggested that lncRNA-21A can control the proliferation of human tumor cell lines, possibly through regulation of CENP-F expression. However, little is known whether lncRNA-21A plays a role in breast cancer. In this study, we reported that lncRNA-21A is downregulated in breast cancer, as detected by RT-PCR analysis of breast cancer tissue scan, suggesting its possible role as a tumor suppressor. In consistent with this finding, lncRNA-21A promotes apoptosis and attenuates cell invasion ability in breast cancer cells. Western blot revealed that overexpression of lncRNA-21A can reduce the phosphorylation of Akt in MCF-7 cells. To determine its underlying mechanism, we performed RNA precipitation assays with the synthetic biotin labeled lncRNA-21A RNA probe followed by mass spectrometry analysis, and we identified hnRNP U and EWS as binding partners for lncRNA-21A. Suppression of EWS by RNAi leads to a reduced level of phosphorylated Akt, suggesting its role in lncRNA-21A-medited Akt activity. Of great interest, we found that like microRNAs, lncRNA-21A can also be secreted through exosomes into conditioned medium. Furthermore, the secreted lncRNA-21A from normal breast epithelial cells can be functionally taken up by recipient metastatic breast cancer cells, suppressing the cell invasion. Together, these results suggest that as a potential tumor suppressor, lncRNA-21A may be used by the host through exosome-mediated gene transfer as a defense mechanism against invasive tumor cells. Citation Format: Ramesh Singh, Yin-yuan Mo. LncRNA-21a is a potential tumor suppressor in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3555. doi:10.1158/1538-7445.AM2014-3555