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Cancer Lett. 2016 Jul 1;376(2):293-302. doi: 10.1016/j.canlet.2016.04.011. Epub 2016 Apr 11.

MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis.

Author information

1
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361105, China.
2
Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, China. Electronic address: j.s.pan76@gmail.com.
3
Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, China.
4
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361105, China. Electronic address: cxiao@scripps.edu.
5
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361105, China. Electronic address: jhan@xmu.edu.cn.

Abstract

The miR-17~92 microRNA (miRNA) cluster host gene is upregulated in a broad spectrum of human cancers including colorectal cancer (CRC). Previous studies have shown that miR-17~92 promotes tumorigenesis and cancer angiogenesis in some tumor models. However, its role in the initiation and progression of CRC remains unknown. In this study, we found that transgenic mice overexpressing miR-17~92 specifically in epithelial cells of the small and large intestines exhibited decreased tumor size and tumor angiogenesis in azoxymethane and dextran sulfate sodium salt (AOM-DSS)-induced CRC model as compared to their littermates control. Further study showed that miR-17~92 inhibited the progression of CRC via suppressing tumor angiogenesis through targeting multiple tumor angiogenesis-inducing genes, TGFBR2, HIF1α, and VEGFA in vivo and in vitro. Collectively, we demonstrated that miR-17~92 suppressed tumor progression by inhibiting tumor angiogenesis in a genetically engineered mouse model, indicating the presence of cellular context-dependent pro- and anti-cancer effects of miR-17~92.

KEYWORDS:

Colorectal cancer; HIF1α; MiR-17~92; TGFBR2; VEGFA

PMID:
27080303
DOI:
10.1016/j.canlet.2016.04.011
[Indexed for MEDLINE]

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