Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma.
Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma.
复制标题
Twist1相关的miR-26b-5p通过靶向肝细胞癌中的SMAD1抑制上皮间质转化、迁移和侵袭
DOI：
10.18632/oncotarget.8328
复制
发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
An J
中科院分区：
文献类型：
--
作者：
Wang Y;Sun B;Zhao X;Zhao N;Sun R;Zhu D;Zhang Y;Li Y;Gu Q;Dong X;Wang M;An J
Twist 1是一种诱导上皮-间质转化（EMT）和促进肿瘤转移的基因。微小RNA（miRNAs）参与EMT过程并与肝细胞癌（HCC）的转移相关。在本研究中，使用微阵列，与HepG 2载体细胞系相比，HepG 2-Twist 1 HCC细胞系中microRNA-26 b-5 p（miR-26 b-5 p）表达持续且显著下调（HepG 2-Twist 1细胞系可以稳定表达Twist 1）。通过ChIP-seq技术，发现Twist 1通过与miR-26 b-5 p的启动子区结合，直接介导miR-26 b-5 p在HepG 2-Twist 1细胞中的下调。功能获得和功能丧失研究均显示，miR-26 b-5 p在体外显著抑制HCC细胞的EMT和侵袭能力。使用小鼠模型，与对照组相比，来自miR-26 b-5 p过表达的HCC细胞的肿瘤显示出致瘤性显著降低。随后的研究表明，miR-26 b-5 p直接抑制SMAD家族成员1（SMAD 1）的表达。miR-26 b-5 p在SMAD 1抑制后抑制BMP 4/Smad 1信号传导。SMAD 1的过表达逆转了miR-26 b-5 p的功能。在人HCC组织和小鼠异种移植肿瘤中，miR-26 b-5 p水平与SMAD 1表达以及转移呈负相关。结论：miR-26 b-5 p通过靶向SMAD 1和BMP 4/Smad 1信号通路抑制Twist 1诱导的肝癌细胞EMT、侵袭和转移。这表明miR-26 b-5 p在抗HCC治疗中有希望的应用。
Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis. Conclusion: miR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy.
登录
查看更多内容
影响因子：
3.8
作者：
Matsuo N;Shiraha H;Fujikawa T;Takaoka N;Ueda N;Tanaka S;Nishina S;Nakanishi Y;Uemura M;Takaki A;Nakamura S;Kobayashi Y;Nouso K;Yagi T;Yamamoto K
通讯作者：
Yamamoto K
影响因子：
13
作者：
Eivers, Edward;Demagny, Hadrien;De Robertis, E. M.
通讯作者：
De Robertis, E. M.
影响因子：
--
作者：
Liu CW;Li CH;Peng YJ;Cheng YW;Chen HW;Liao PL;Kang JJ;Yeng MH
通讯作者：
Yeng MH
影响因子：
3.7
作者：
Li A;Xia X;Yeh J;Kua H;Liu H;Mishina Y;Hao A;Li B
通讯作者：
Li B
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko