MiR-199a regulates cell proliferation and survival by targeting FZD7.
MiR-199a regulates cell proliferation and survival by targeting FZD7.
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DOI：
10.1371/journal.pone.0110074
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Song J;Gao L;Yang G;Tang S;Xie H;Wang Y;Wang J;Zhang Y;Jin J;Gou Y;Yang Z;Chen Z;Wu K;Liu J;Fan D
越来越多的证据表明，miRNAs是多种细胞过程的重要调控因子，当miRNAs在不同类型的肿瘤如肝细胞癌（HCC）中异常表达时，在肿瘤的发生和发展中发挥重要作用。发现miR-199 a-5 p（也称为miR-199 a）的异常表达有助于不同类型癌症（包括HCC）的致癌作用。然而，精确的分子机制尚未完全理解。目前的研究表明，miR-199 a在HCC组织和细胞中频繁下调。重要的是，miR-199 a的低表达与HCC的恶性潜能和不良预后显著相关，并且miR-199 a在HCC细胞中的恢复导致体外和体内细胞增殖和细胞周期的抑制。此外，Frizzled type 7 receptor（FZD 7），参与癌症发展和进展的最重要的Wnt受体，被鉴定为miR-199 a的功能靶标。此外，FZD 7与miR-199 a在HCC组织和细胞中的表达呈负相关，并且miR-199 a的过表达可显著下调FZD 7下游基因的表达，包括β-catenin、Jun、Cyclin D1和Myc，进一步加强了这些发现。总之，这些发现不仅有助于我们从一个新的角度更好地阐明肝癌发生的分子机制，而且还为进一步研究miR-199 a作为一种潜在的生物标志物和一种有前途的肝癌治疗方法提供了新的理论基础。
A growing amount of evidence indicates that miRNAs are important regulators of multiple cellular processes and, when expressed aberrantly in different types of cancer such as hepatocellular carcinoma (HCC), play significant roles in tumorigenesis and progression. Aberrant expression of miR-199a-5p (also called miR-199a) was found to contribute to carcinogenesis in different types of cancer, including HCC. However, the precise molecular mechanism is not yet fully understood. The present study showed that miR-199a is frequently down-regulated in HCC tissues and cells. Importantly, lower expression of miR-199a was significantly correlated with the malignant potential and poor prognosis of HCC, and restoration of miR-199a in HCC cells led to inhibition of the cell proliferation and cell cycle in vitro and in vivo. Furthermore, Frizzled type 7 receptor (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-199a. In addition, these findings were further strengthened by results showing that expression of FZD7 was inversely correlated with miR-199a in both HCC tissues and cells and that over-expression of miR-199a could significantly down-regulate the expression of genes downstream of FZD7, including β-catenin, Jun, Cyclin D1 and Myc. In conclusion, these findings not only help us to better elucidate the molecular mechanisms of hepatocarcinogenesis from a fresh perspective but also provide a new theoretical basis to further investigate miR-199a as a potential biomarker and a promising approach for HCC treatment.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Gramantieri, Laura;Ferracin, Manuela;Negrini, Massimo
通讯作者：
Negrini, Massimo
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW
影响因子：
11.5
作者：
Lee, Jeong-Won;Choi, Chel Hun;Bae, Duk-Soo
通讯作者：
Bae, Duk-Soo