microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2
Wenting Liao,Tingting Li,Zheng-Gen Wang,Shu-Yang Wang,Mei-Rong He,Ya-Ping Ye,Lu Qi,Yan-Mei Cui,Ping Wu,Hong-Li Jiao,Chi Zhang,Yi-Jun Xie,Jun-Xian Wang,Yanqing Ding +13 more
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TLDR
Functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHL PP2 in the pathogenesis of colorectal cancer are revealed.Abstract:
Purpose: To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer. Experimental Design: Real-time PCR was used to quantify miR-224 expression. The association of miR-224 with the clinicopathologic features and survival was evaluated in 110 colorectal cancer patients. The role of miR-224 in colorectal cancer was investigated using in vitro and in vivo assays. Luciferase reporter assays were conducted to confirm target gene associations. Results: miR-224 was overexpressed in colorectal cancer. High-level expression of miR-224 was significantly associated with an aggressive phenotype and poor prognosis. Overexpression of miR-224 promoted colorectal cancer cell proliferation in vitro and tumor growth in vivo . Specifically, miR-224 accelerated the G 1 –S phase transition through activation of AKT/FOXO3a signaling, downregulation of p21Cip1 and p27Kip1, and upregulation of cyclin D1. Moreover, both PH domain leucine-rich-repeats protein phosphatase 1 ( PHLPP1 ) and PHLPP2 , antagonists of PI3K/AKT signaling, were confirmed as bona fide targets of miR-224. miR-224 directly targeted the 3′-untranslated regions of the PHLPP1 and PHLPP2 mRNAs and repressed their expression. Conclusion: This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer. miR-224 not only plays important roles in the regulation of cell proliferation and tumor growth in colorectal cancer, but also has potential as a prognostic marker or therapeutic target for colorectal cancer. Clin Cancer Res; 19(17); 4662–72. ©2013 AACR .read more
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Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin.
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The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis
Hui Ling,Karen Pickard,Cristina Ivan,Claudio Isella,Mariko Ikuo,Mariko Ikuo,Richard Mitter,Riccardo Spizzo,Marc D. Bullock,Marc D. Bullock,Cornelia Braicu,Valentina Pileczki,Kimberly Vincent,Martin Pichler,Martin Pichler,Verena Stiegelbauer,Gerald Hoefler,Maria Inês Almeida,Annie Hsiao,Xinna Zhang,John N. Primrose,Graham Packham,Kevin Liu,Krishna Bojja,Roberta Gafà,Lianchun Xiao,Simona Rossi,Jian H. Song,Ivan Vannini,Francesca Fanini,Scott Kopetz,Patrick A. Zweidler-McKay,Xuemei Wang,Calin Ionescu,Alexandru Irimie,Muller Fabbri,Giovanni Lanza,Stanley R. Hamilton,Ioana Berindan-Neagoe,Ioana Berindan-Neagoe,Enzo Medico,Alex H. Mirnezami,George A. Calin,Milena S. Nicoloso,Milena S. Nicoloso +44 more
TL;DR: MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC and promotes CRC metastasis, at least in part, through the regulation of SMAD4.
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MicroRNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity
TL;DR: Recent evidence demonstrating the potential role of miRNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC are reviewed.
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