miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1.

miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1.
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miR-1207-5p 通过靶向 CSF1 抑制肺癌生长和转移

DOI:
10.18632/oncotarget.8718
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发表时间:
2016-05-31
期刊:
影响因子:
--
通讯作者:
Ma J
Ma J
中科院分区:
其他
文献类型:
--
作者:
Dang W;Qin Z;Fan S;Wen Q;Lu Y;Wang J;Zhang X;Wei L;He W;Ye Q;Yan Q;Li G;Ma J

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我们先前曾报道miR-1207-5p能抑制表皮生长因子和转化生长因子-β等生长因子诱导的上皮-间充质转化,但其确切机制尚不清楚。在此,我们鉴定了克隆刺激因子1(CSF1)是miR-1207-5p的靶基因。CSF1控制巨噬细胞的产生、分化和功能,并促进促炎趋化因子的释放。我们发现miR-1207-5p在体外抑制肺癌细胞A549的增殖、迁移和侵袭,并抑制STAT3和AKT信号转导。MIR-1207-5p过表达可促进HUVEC血管生成,并调节巨噬细胞M2表型。在裸鼠移植瘤模型中,MIR-1207-5P也能显著抑制A549细胞的转移。应用肺癌组织芯片检测MIR-1207-5p和CSF1的表达水平及其与肺癌生存和转移状态的关系。巨噬细胞是肿瘤微环境的重要组成部分,因此miR-1207-5p-CSF1轴可能通过调节肿瘤微环境而成为肺癌发生发展的新调节因子。
We previously reported that miR-1207-5p can inhibit epithelial-mesenchymal transition (EMT) induced by growth factors such as EGF and TGF-β, but the exact mechanism is unclear. Here we identified that Colony stimulating factor 1 (CSF1) is a target gene of miR-1207-5p. CSF1 controls the production, differentiation and function of macrophage and promotes the release of proinflammatory chemokines. We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings. miR-1207-5p overexpression can increase HUVEC angiogenesis, and can modulate the M2 phenotype of macrophage. miR-1207-5p also significantly inhibited A549 cells metastasis in a nude mouse xenograft model. miR-1207-5p and CSF1 expression levels and their relationship with lung cancer survival and metastasis status were assayed by means of a lung cancer tissue microarray. Macrophage is an essential part of the tumor microenvironment, thus the miR-1207-5p-CSF1 axis maybe a new regulator of lung cancer development through modulating the tumor microenvironment.
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