American Association for Cancer Research
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Supplementary Figure 3 from microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

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journal contribution
posted on 2023-03-31, 17:20 authored by Wen-Ting Liao, Ting-Ting 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, Yan-Qing Ding

Supplementary Figure 3 - PDF file 63K, Supplementary Fig.S3. Overexpression of PHLPP1 or PHLPP2 abrogated the miR-224-mediated regulation of of the cell-cycle regulators



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 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.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.