Blockage of TGFβ-SMAD2 by demethylation-activated miR-148a is involved in caffeic acid-induced inhibition of cancer stem cell-like properties in vitro and in vivo.
Blockage of TGFβ-SMAD2 by demethylation-activated miR-148a is involved in caffeic acid-induced inhibition of cancer stem cell-like properties in vitro and in vivo.
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去甲基化激活的 miR-148a 对 TGFbeta-SMAD2 的阻断参与了咖啡酸诱导的体外和体内癌症干细胞样特性的抑制。
DOI：
10.1016/j.fob.2015.05.009
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发表时间：
2015
期刊：
影响因子：
2.6
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Li, Yuan;Jiang, Fei;Chen, Lijun;Yang, Ye;Cao, Shuyuan;Ye, Yuting;Wang, Xingxing;Mu, Juan;Li, Zhong;Li, Lei
关键词：
咖啡酸（CaA）减弱人类癌细胞中的CSC样特性。CaA抑制SMAD 2的活性/表达。CaA通过诱导DNA去甲基化而提高miR-148 a的表达。miR-148 a在Ca A处理的细胞中靶向SMAD 2。CaA通过miR-148 a减弱CSC样性质。由于癌症干细胞（CSC）介导的复发，目前用于治疗癌症的标准实践不太令人满意。咖啡酸（CaA）是一种新型的抗肿瘤药物，可抑制人类癌细胞的增殖、迁移和侵袭。然而，关于CaA在调控CSC样特性中的功能及其可能的分子机制还知之甚少。在此，我们发现CaA通过microRNA-148 a（miR-148 a）介导的转化生长因子β（TGFβ）-SMAD 2信号通路的抑制，在体外和体内均减弱了CSC样特性。CaA通过诱导DNA甲基化增强miR-148 a的表达。靶向SMAD 2 -3′UTR的miR-148 a可降低SMAD 2的表达。miR-148 a的敲除可消除Ca A对TGFβ-SMAD 2信号通路的抑制作用，并可使细胞具有CSC样特性。我们的研究发现了CaA通过miR-148 a介导的TGFβ-SMAD 2信号通路抑制CSCs样特性的新机制，这可能有助于发现治疗人类癌症的新途径。
Caffeic acid (CaA) attenuates CSCs-like properties in human cancer cells. CaA inhibits the activity/expression of SMAD2. CaA elevates the expression of miR-148a by inducing DNA demethylation. miR-148a targets SMAD2 in CaA-treated cells. CaA attenuates CSCs-like properties via miR-148a. Current standard practices for treatment of cancers are less than satisfactory because of recurrence mediated by cancer stem cells (CSCs). Caffeic acid (CaA) is a novel anti-tumor agent that inhibits proliferation, migration, and invasion in human cancer cells. However, little is known about the functions of CaA in regulating CSCs-like properties and the potential molecular mechanisms. Here, we found that CaA attenuated the CSCs-like properties by the microRNA-148a (miR-148a)-mediated inhibition of transforming growth factor beta (TGFβ)-SMAD2 signaling pathway both in vitro and in vivo. CaA enhanced the expression of miR-148a by inducing DNA methylation. MiR-148a, which targeted the SMAD2-3′UTR, decreased the expression of SMAD2. Knockdown of miR-148a abolished the CaA-induced inhibition of TGFβ-SMAD2 signal pathway and the CSCs-like properties. Our study found a novel mechanism that CaA inhibits the CSCs-like properties via miR-148a-mediated inhibition of TGFβ-SMAD2 signaling pathway, which may help to identify a new approach for the treatment of human cancers.
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影响因子：
4.7
作者：
Lu, Lingeng;Katsaros, Dionyssios;Yu, Herbert
通讯作者：
Yu, Herbert
DOI：
10.1093/jnci/dji039
发表时间：
2005-02-16
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Michels, KB;Willett, WC;Giovannucci, E
通讯作者：
Giovannucci, E
影响因子：
8.4
作者：
Bueno, Lorea;de Alwis, Dinesh P.;Troconiz, Inaki F.
通讯作者：
Troconiz, Inaki F.
影响因子：
8.4
作者：
Lu, Lingeng;Katsaros, Dionyssios;Yu, Herbert
通讯作者：
Yu, Herbert
影响因子：
4.7
作者：
Jung, Joo Eun;Kim, Hong Sook;Chung, Myung-Hee
通讯作者：
Chung, Myung-Hee