MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1.
MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1.
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MicroRNA-520b 通过靶向 MEKK2 和 Cyclin D1 抑制肝癌细胞的生长
DOI：
10.1371/journal.pone.0031450
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Zhang W;Kong G;Zhang J;Wang T;Ye L;Zhang X
越来越多的证据表明，microRNAs （miRNAs）的失调有助于肿瘤的发生。我们之前发现microRNA-520b （miR-520b）参与了乳腺癌细胞的补体攻击和迁移。在本报告中，我们发现miR-520b是肝细胞癌（HCC）发展中的重要miRNA。我们的数据显示，miR-520b在临床HCC组织和肝癌细胞系中的表达水平显著降低。通过集落形成实验、5-乙基-2-脱氧尿苷（EdU）结合实验和3-（4,5-二甲基噻唑-2-酰基）-2,5-二苯基溴化四唑（MTT）实验，我们观察到miR-520b的引入显著抑制了肝癌细胞的生长。此外，miR-520b的异位表达能够抑制裸鼠肝癌细胞的生长。进一步研究发现，有丝分裂原活化蛋白激酶激酶2 （MEKK2）和细胞周期蛋白D1是miR-520b的两个直接靶基因。在体外和体内，沉默MEKK2或cyclin D1均能抑制肝癌细胞的生长，这与miR-520b过表达对肝癌细胞生长的影响是一致的。此外，miR-520b显著降低了c-Jun n -末端激酶（p-JNK， MEKK2的下游效应物）或视网膜母细胞瘤（p-Rb， cyclin D1的下游效应物）的磷酸化水平。综上所述，在体外和体内，miR-520b能够通过靶向MEKK2或cyclin D1抑制肝癌细胞的生长。我们的研究结果为miR-520b在HCC发展中的作用提供了新的见解，并暗示了miR-520b在癌症治疗中的潜在应用。
Growing evidence indicates that the deregulation of microRNAs (miRNAs) contributes to the tumorigenesis. We previously revealed that microRNA-520b (miR-520b) was involved in the complement attack and migration of breast cancer cells. In this report, we show that miR-520b is an important miRNA in the development of hepatocellular carcinoma (HCC). Our data showed that the expression levels of miR-520b were significantly reduced in clinical HCC tissues and hepatoma cell lines. We observed that the introduction of miR-520b dramatically suppressed the growth of hepatoma cells by colony formation assays, 5-ethynyl-2-deoxyuridine (EdU) incorporation assays and 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, ectopic expression of miR-520b was able to inhibit the growth of hepatoma cells in nude mice. Further studies revealed that the mitogen-activated protein kinase kinase kinase 2 (MEKK2) and cyclin D1 were two of direct target genes of miR-520b. Silencing of MEKK2 or cyclin D1 was able to inhibit the growth of hepatoma cells in vitro and in vivo, which is consistent with the effect of miR-520b overexpression on the growth of hepatoma cells. In addition, miR-520b significantly decreased the phosphorylation levels of c-Jun N-terminal kinase (p-JNK, a downstream effector of MEKK2) or retinoblastoma (p-Rb, a downstream effector of cyclin D1). In conclusion, miR-520b is able to inhibit the growth of hepatoma cells by targeting MEKK2 or cyclin D1 in vitro and in vivo. Our findings provide new insights into the role of miR-520b in the development of HCC, and implicate the potential application of miR-520b in cancer therapy.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
--
作者：
Noonan EJ;Place RF;Basak S;Pookot D;Li LC
通讯作者：
Li LC
影响因子：
4.8
作者：
Su, B;Cheng, JK;Guo, ZJ
通讯作者：
Guo, ZJ
影响因子：
50.3
作者：
Garofalo M;Di Leva G;Romano G;Nuovo G;Suh SS;Ngankeu A;Taccioli C;Pichiorri F;Alder H;Secchiero P;Gasparini P;Gonelli A;Costinean S;Acunzo M;Condorelli G;Croce CM
通讯作者：
Croce CM
DOI：
10.1073/pnas.081021898
发表时间：
2001-04-10
影响因子：
11.1
作者：
Chayama, K;Papst, PJ;Gelfand, EW
通讯作者：
Gelfand, EW