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

• Published in: Cancer letters Vol. 409; pp. 104 - 115
• Main Authors: Sun, Li-Na, Zhi, Zheng, Chen, Liang-Yan, Zhou, Qun, Li, Xiu-Ming, Gan, Wen-Juan, Chen, Shu, Yang, Meng, Liu, Yao, Shen, Tong, Xu, Yong, Li, Jian-Ming
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.11.2017; Elsevier Limited
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - metabolism; Acetyl-CoA C-Acyltransferase - metabolism; Activator protein 1; Acyl-CoA oxidase; Animals; Apoptosis; Breast cancer; Caco-2 Cells; Cancer metastasis; Carbon-Carbon Double Bond Isomerases - metabolism; Cell Line, Tumor; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Deacetylation; Enoyl-CoA Hydratase - metabolism; Experiments; Fatty-acid oxidation; Gene silencing; HCT116 Cells; Heterografts; HT29 Cells; Humans; Lung cancer; Metabolism; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Metastasis; Oxidation; Proteins; Racemases and Epimerases - metabolism; Rodents; Signal Transduction; SIRT1; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Transcription factors; Transcription, Genetic; Transfection; Tumors; Xenografts; China; Fatty-acid oxidation; microRNA; Cancer metastasis; SIRT1; Colorectal cancer
• DOI: 10.1016/j.canlet.2017.09.001
• ISSN: 0304-3835; 1872-7980

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. •SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.