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Cancer Lett. 2017 Nov 28;409:104-115. doi: 10.1016/j.canlet.2017.09.001. Epub 2017 Sep 18.

SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p.

Author information

1
Department of Pathology and Pathophysiology, Medical College of Soochow University, Soochow University, Suzhou 215123, People's Republic of China.
2
First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215123, People's Republic of China.
3
Department of Clinical Medicine, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
4
Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, People's Republic of China. Electronic address: yxu2005@gmail.com.
5
Department of Pathology and Pathophysiology, Medical College of Soochow University, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: jianmingli@suda.edu.cn.

Abstract

The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.

KEYWORDS:

Cancer metastasis; Colorectal cancer; Fatty-acid oxidation; SIRT1; microRNA

PMID:
28923398
DOI:
10.1016/j.canlet.2017.09.001
[Indexed for MEDLINE]

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