Details

Autor(en) / Beteiligte

• LIAO, Wen-Ting
• LI, Ting-Ting
• CHI ZHANG
• XIE, Yi-Jun
• WANG, Jun-Xian
• DING, Yan-Qing
• WANG, Zheng-Gen
• WANG, Shu-Yang
• HE, Mei-Rong
• YE, Ya-Ping
• LU QI
• CUI, Yan-Mei
• PING WU
• JIAO, Hong-Li

Titel

microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

Ist Teil von

• Clinical cancer research, 2013-09, Vol.19 (17), p.4662-4672

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer. 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. 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 G1-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. 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.