دورية أكاديمية
Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a.
العنوان: | Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a. |
---|---|
المؤلفون: | Huanxin Lin, Ting Dai, Huaping Xiong, Xiaohui Zhao, Xiuting Chen, Chunping Yu, Jun Li, Xi Wang, Libing Song |
المصدر: | PLoS ONE, Vol 5, Iss 12, p e15797 (2010) |
بيانات النشر: | Public Library of Science (PLoS), 2010. |
سنة النشر: | 2010 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27(Kip1) and p21(Cip1), and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3'-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 46632751 |
Relation: | http://europepmc.org/articles/PMC3009749?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0015797 |
URL الوصول: | https://doaj.org/article/41db466327514575b217bb27916158a5 |
رقم الأكسشن: | edsdoj.41db466327514575b217bb27916158a5 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 46632751 |
---|---|
DOI: | 10.1371/journal.pone.0015797 |