SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p
SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p
复制标题
SIRT1 通过转录抑制 miR-15b-5p 抑制结直肠癌转移
DOI：
10.1016/j.canlet.2017.09.001
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发表时间：
2017-11-28
期刊：
影响因子：
9.7
通讯作者：
Li, Jian-Ming
中科院分区：
文献类型：
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作者：
Sun, Li-Na;Zhi, Zheng;Li, Jian-Ming
III类去乙酰化酶sirtuin 1（SIRT 1）是sirtuin家族蛋白的一员，在包括结直肠癌（CRC）在内的许多类型的癌症中起着关键作用。在这里，我们报告了SIRTI抑制CRC转移在体外和体内作为一个负调控miR-15 b-5 p转录。从机制上讲，SIRTI通过AP-1的脱乙酰化削弱了激活蛋白（AP-1）对miR-15 b-5 p反式激活的调节作用。重要的是，脂肪酸氧化（FAO）途径的关键酶酰基辅酶A氧化酶1（ACOX 1）被发现是miR-15 b-5 p的直接靶点。SIRTI表达与CRC细胞和异种移植物中的ACOX 1表达呈正相关。此外，ACOX 1过表达减弱了miR-15 b-5 p过表达对CRC细胞迁移和侵袭的增强作用。总之，我们的研究证明了SIRTI/miR-15 b-5 p/ACOXI轴在CRC转移中的功能作用，并提出了转移性CRC治疗的潜在靶点。(C)2017爱思唯尔B. V.保留所有权利。
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 SIRTI suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRTI 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. SIRTI 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 SIRTI/miR-15b-5p/ACOXI axis in CRC metastasis and suggested a potential target for metastatic CRC therapy. (C) 2017 Elsevier B.V. All rights reserved.