MiR-214 and N-ras regulatory loop suppresses rhabdomyosarcoma cell growth and xenograft tumorigenesis.
MiR-214 and N-ras regulatory loop suppresses rhabdomyosarcoma cell growth and xenograft tumorigenesis.
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MiR-214 和 N-ras 调节环抑制横纹肌肉瘤细胞生长和异种移植肿瘤发生。
DOI：
10.18632/oncotarget.1855
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发表时间：
2014-04-30
期刊：
影响因子：
--
通讯作者：
Cheng SY
中科院分区：
文献类型：
--
作者：
Huang HJ;Liu J;Hua H;Li SE;Zhao J;Yue S;Yu TT;Jin YC;Cheng SY
横纹肌肉瘤（RMS）是一种儿童恶性软组织癌，来源于永久性生长的肌源性祖细胞。在这里，我们报告了miR-214在人RMS细胞系中显著下调。虽然不是小鼠胚胎发生所必需的，但miR-214抑制小鼠胚胎成纤维细胞（MEF）增殖。当重新引入RD细胞（一种人胚胎RMS细胞系）中时，miR-214显示出抑制肿瘤细胞生长、诱导肌源性分化和凋亡以及抑制集落形成和异种移植肿瘤发生。我们发现，在缺乏miR-214的情况下，原癌基因N-ras的表达在miR-214−/− MEFs中显著升高，并且在RD细胞中使用microRNA模拟物或抑制剂操纵miR-214水平会改变N-ras的表达。我们进一步证明，从缺乏其3 '-非翻译区的cDNA强制表达N-ras中和了miR-214的促肌生成和抗增殖活性。最后，我们发现N-ras是miR-214抑制异种移植肿瘤生长的保守靶点，并且N-ras表达在异种移植肿瘤模型以及实际的人RMS组织切片中上调。总之，这些数据表明miR-214是人RMS肿瘤发生的真正抑制剂。
Rhabdomyosarcoma (RMS) is a childhood malignant soft tissue cancer that is derived from myogenic progenitors trapped in a permanent mode of growth. Here, we report that miR-214 is markedly down-regulated in human RMS cell lines. Although not required for embryogenesis in mice, miR-214 suppresses mouse embryonic fibroblast (MEF) proliferation. When re-introduced into RD cells, a line of human embryonal RMS cells, miR-214 showed inhibition of tumor cell growth, induction of myogenic differentiation and apoptosis, as well as suppression of colony formation and xenograft tumorigenesis. We show that in the absence of miR-214, expression of proto-oncogene N-ras is markedly elevated in miR-214−/− MEFs, and manipulations of miR-214 levels using microRNA mimics or inhibitor in RD cells reciprocally altered N-ras expression. We further demonstrate that forced expression of N-ras from a cDNA that lacks its 3'-untranslated region neutralized the pro-myogenic and anti-proliferative activities of miR-214. Finally, we show that N-ras is a conserved target of miR-214 in its suppression of xenograft tumor growth, and N-ras expression is up-regulated in xenograft tumor models as well as actual human RMS tissue sections. Taken together, these data indicate that miR-214 is a bona fide suppressor of human RMS tumorigensis.
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影响因子：
5.6
作者：
PIGAULT, C;FOLLENIUSWUND, A;BRISSON, A
通讯作者：
BRISSON, A
影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
MiR-214依赖性调节骨骼肌和胚胎干细胞中Polycomb蛋白EZH2的调节。
影响因子：
16
作者：
Juan, Aster H.;Kumar, Roshan M.;Marx, Joseph G.;Young, Richard A.;Sartorelli, Vittorio
通讯作者：
Sartorelli, Vittorio
影响因子：
11.2
作者：
Croci, S;Landuzzi, L;Lollini, PL
通讯作者：
Lollini, PL
影响因子：
8
作者：
Nitzki, F.;Zibat, A.;Hahn, H.
通讯作者：
Hahn, H.