miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin
miR-409-3p inhibits HT1080 cell proliferation, vascularization and metastasis by targeting angiogenin
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DOI：
10.1016/j.canlet.2012.04.010
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发表时间：
2012-10-28
期刊：
影响因子：
9.7
通讯作者：
Xu, Zhengping
中科院分区：
文献类型：
--
作者：
Weng, Chunhua;Dong, Haojie;Xu, Zhengping
血管生成素（angiogenin，ANG）是一种血管生成和致瘤因子，在多种肿瘤中表达增高，但其调控机制尚不清楚。在本研究中，硅胶搜索预测miR-409- 3 p靶向ANG mRNA的3'非翻译区（3' UTR）。miR-409- 3 p在纤维肉瘤HT 1080细胞中的过表达导致ANG转录和ANG产生的稳态水平降低，这是通过该miRNA与ANG 3 'UTR的直接结合实现的。miR-409- 3 p对rRNA转录、细胞增殖和血管生成拟态的抑制作用可通过在ANG 3 'UTR内具有突变的miR-409- 3 p结合位点的ANG过表达而部分恢复。miR-409- 3 p在移植的HT 1080细胞中的异位表达导致小鼠肿瘤异种移植物中肿瘤生长、血管形成和肺转移的延迟。在这些异种移植组织中，miR-409- 3 p的表达与ANG呈负相关，这在人纤维肉瘤样品中也检测到。此外，miR-409- 3 p在体外对人脐静脉内皮细胞的增殖和血管生成也有抑制作用。总之，这些数据表明miR-409- 3 p通过下调ANG表达来抑制肿瘤生长、血管形成和转移。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Although the expression of angiogenin (ANG), an angiogenic and tumorigenic factor, is elevated in various types of cancers, its regulation mechanism remains unclear. In the present study, in silica search predicted that miR-409-3p targeted to the 3' untranslated region (3'UTR) of the ANG mRNA. Overexpression of miR-409-3p in fibrosarcoma HT1080 cells resulted in decreased steady-state level of ANG transcript and ANG production which were achieved through direct binding of this miRNA to the ANG 3'UTR. The suppressions of miR-409-3p to rRNA transcription, cell proliferation and vasculogenic mimicry could be partially restored by overexpression of ANG with a mutated binding site of miR-409-3p within the ANG 3'UTR. Ectopic expression of miR-409-3p in transplanted HT1080 cells led to the retardation of tumor growth, vascularization and lung metastasis in mouse tumor xenografts. In these xenografts tissues, the expression of miR-409-3p displayed an inverse correlation with ANG, which was also detected in human fibrosarcoma samples. In addition, the suppression effects of miR-409-3p on cell proliferation and angiogenesis in vitro were also found in human umbilical vein endothelial cells. Taken together, these data demonstrate that miR-409-3p inhibits tumor growth, vascularization and metastasis through down-regulating ANG expression. (c) 2012 Elsevier Ireland Ltd. All rights reserved.