MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis.
MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis.
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MiR-590-5p通过调节核因子90/血管内皮生长因子A轴抑制结直肠癌血管生成和转移
DOI：
10.1038/cddis.2016.306
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发表时间：
2016-10-13
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
MicroRNA-590-5p(miR-590-5p)的表达改变与肿瘤的发生有关，但其在结直肠癌中的作用尚不清楚。在这项研究中，我们重点研究了miR-590-5p在癌细胞和正常细胞中不同表达水平的影响。结果表明，miR-590-5p在人结直肠癌细胞和组织中的表达水平低于正常对照细胞和组织。同样，在我们的异种移植小鼠模型中，miR-590-5p的敲除促进了结直肠癌的进展。然而，miR-590-5p在小鼠中的过表达抑制了血管生成、肿瘤生长和肺转移。核因子90(NF90)是血管内皮细胞生长因子(VEGF)mRNA稳定性和蛋白质合成的正调控因子，是miR-590-5p的直接靶点。NF90的过表达恢复了VEGFA的表达，挽救了miR-590-5P所致的肿瘤血管生成的缺失。相反，NF90-shRNA减弱了miR-590-5P抑制剂导致的肿瘤进展加快。临床上，大肠癌组织中miR-590-5p的表达水平与NF90、VEGFA的表达水平呈负相关。此外，NF90基因的敲除导致pri-miR-590减少，成熟miR-590-5p增加，提示miR-590-5p与NF90之间存在负反馈循环。总之，这些数据证实miR-590-5P是一种抗肿瘤的miR，通过涉及NF90/VEGFA信号轴的新机制抑制结直肠癌血管生成和转移，突显了miR-590-5P作为人类结直肠癌治疗靶点的潜力。
Altered expression of microRNA-590-5p (miR-590-5p) is involved in tumorigenesis, however, its role in colorectal cancer (CRC) remains to be determined. In this study, we focused on examining the effects of different expression levels of miR-590-5p in cancer cells and normal cells. Results showed that there are lower expression levels of miR-590-5p in human CRC cells and tissues than in normal control cells and tissues. Similarly, in our xenograft mouse model, knockdown of miR-590-5p promoted the progression of CRC. However, an overexpression of miR-590-5p in the mice inhibited angiogenesis, tumor growth, and lung metastasis. Nuclear factor 90 (NF90), a positive regulator of vascular endothelial growth factor (VEGF) mRNA stability and protein synthesis, was shown to be a direct target of miR-590-5p. The overexpression of NF90 restored VEGFA expression and rescued the loss of tumor angiogenesis caused by miR-590-5p. Conversely, the NF90-shRNA attenuated the increased tumor progression caused by the miR-590-5p inhibitor. Clinically, the levels of miR-590-5p were inversely correlated with those of NF90 and VEGFA in CRC tissues. Furthermore, knockdown of NF90 lead to a reduction of pri-miR-590 and an increase of mature miR-590-5p, suggesting a negative feedback loop between miR-590-5p and NF90. Collectively, these data establish miR-590-5p as an anti-onco-miR that inhibits CRC angiogenesis and metastasis through a new mechanism involving NF90/VEGFA signaling axis, highlighting the potential of miR-590-5p as a target for human CRC therapy.
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影响因子：
3.7
作者：
Ogata-Kawata H;Izumiya M;Kurioka D;Honma Y;Yamada Y;Furuta K;Gunji T;Ohta H;Okamoto H;Sonoda H;Watanabe M;Nakagama H;Yokota J;Kohno T;Tsuchiya N
通讯作者：
Tsuchiya N
microRNA-497通过靶向血管内皮生长因子-A抑制结直肠癌细胞的侵袭和转移
影响因子：
8.5
作者：
Qiu, Yanyan;Yu, Hui;Yin, Peihao
通讯作者：
Yin, Peihao
影响因子：
5.7
作者：
Suzuki HI;Katsura A;Miyazono K
通讯作者：
Miyazono K
DOI：
10.1504/ijdmb.2015.066332
发表时间：
2015-01-01
影响因子：
0.3
作者：
Pradhan, Meeta;Nagulapalli, Kshithija;Palakal, Mathew
通讯作者：
Palakal, Mathew
影响因子：
5.8
作者：
Das AV;Pillai RM
通讯作者：
Pillai RM