Abstract

Abstract Long non-coding RNAs (LncRNAs) function as oncogenes or tumor suppressors in development and progression of cancer. Chromosome 16q22.1 region is frequently deleted in breast cancer, which may contribute to breast carcinogenesis by inactivation of tumor suppressor genes. This study characterized a new LncRNA tumor suppressor, named p53 activating non-coding RNA (PANCR), located in this Chromosome 16q22.1 region. This PANCR LncRNA consists of 1.5kb in length.Our data showed that PANCR was downregulated in breast cancer cell lines and tissues. In the breast cancer cell lines, PANCR expression appeared reversely correlated with cell malignancy, and in breast cancer tissues, PANCR was downregulated over 2 times in 31(62.0%) of 50 cases when compared to adjacent normal breast tissues. In breast cancer cells MCF7 and immortalized human mammary epithelial cells MCF10A, ectopic expression of PANCR induced marked apoptosis, suppressing cell proliferation in culture and tumor growth in xenografts, but in contrast, shRNA-mediated silencing of PANCR promoted cell growth and proliferation. Mechanistic approaches revealed that in both MCF7 and MCF10A cell, PANCR activated p53 and upregulated pro-apoptotic proteins bid and bim and cell cycle inhibitors p21waf/cip1 and p27Kip1. We further explored the mechanism of action that PANCR activates p53, and our results from RNA immunoprecipitation (RIP), RNA pulldown and immunoprecipitation (Co-IP) demonstrated that the PANCR can bind to p53, dissociate p53-MDM2 complex and thus activate p53.Together our data suggest that the novel LncRNA PANCR located in the deleted Chromosome 16q22.1 region is an intracellular p53activator, functioning as a tumor suppressor by activating p53-mediated apoptosis. Citation Format: Yu Cao. The novel long non-coding RNA PANCR is an intracellular p53 activator [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2572. doi:10.1158/1538-7445.AM2017-2572

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