MicroRNA-370 inhibits the growth and metastasis of lung cancer by down-regulating epidermal growth factor receptor expression.
MicroRNA-370 inhibits the growth and metastasis of lung cancer by down-regulating epidermal growth factor receptor expression.
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MicroRNA-370通过下调表皮生长因子受体表达抑制肺癌生长和转移
DOI：
10.18632/oncotarget.21537
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发表时间：
2017-10-20
期刊：
影响因子：
--
通讯作者：
Wang XC
中科院分区：
文献类型：
--
作者：
Liu X;Huang YG;Jin CG;Zhou YC;Chen XQ;Li J;Chen Y;Li M;Yao Q;Li K;Lan M;Ye JG;Wang XC
microRNA-370（miR-370）异常表达在包括肺癌在内的几种癌症中经常被报道。然而，miR-370在肺癌生长和转移中的作用及其分子机制尚不清楚。在这里，我们发现在大多数人肺癌细胞和非肿瘤细胞中表皮生长因子受体（EGFR）的表达水平较高，但miR-370的表达水平较低。诱导miR-370过表达显著降低XWLC-05和H157细胞中EGFR的表达水平和EGFR 3′非翻译区（UTR）调控的荧光素酶活性，提示miR-370可能与EGFR mRNA的3′UTR结合。与对照组相比，miR-370过表达可显著抑制XWLC-05和H157细胞的增殖、克隆形成能力、迁移和侵袭能力，而miR-370抑制剂过表达可增强XWLC-05和H157细胞的体外肿瘤行为。此外，miR-370过表达可下调XWLC-05和H157细胞中EGFR和缺氧诱导因子（HIF）-1α的表达，并减弱细胞外单调节激酶（ERK）1/2和AKT磷酸化。与此相反，miR 370抑制剂过表达增加XWLC-05和H157细胞中EGFR和HIF-1α的表达以及ERK 1/2和AKT磷酸化。此外，miR-370过表达显著降低EGFR和CD 31表达水平，并抑制小鼠异种移植NSCLC肿瘤的生长和肺转移。我们的研究表明，miR-370可能通过与EGFR的3′UTR结合，下调ERK 1/2和AKT信号通路，从而抑制EGFR的表达，抑制非小细胞肺癌的生长、血管生成和转移。
Abnormal microRNA-370 (miR-370) expression has been frequently reported in several types of cancers, including lung cancer. However, the role and molecular mechanisms of miR-370 in regulating the growth and metastasis of lung cancer have not been clarified. Here, we show higher levels of epidermal growth factor receptor (EGFR), but lower levels of miR-370 expression in most human lung cancer cells and non-tumor cells. Induction of miR-370 over-expression significantly reduced the levels of EGFR expression and the EGFR 3′untranslated region (UTR)-regulated luciferase activity in XWLC-05 and H157 cells, suggesting that miR-370 may bind to the 3′UTR of EGFR mRNA. Compared with the control cells, induction of miR370 overexpression significantly inhibited the proliferation, clone formation capacity, migration and invasion of XWLC-05 and H157 cells while miR-370 inhibitor over-expression enhanced their tumor behaviors in vitro. Furthermore, miR-370 over-expression down-regulated the EGFR and hypoxia-inducible factor (HIF)-1α expression, and attenuated the extracellular single-regulated kinase (ERK)1/2 and AKT phosphorylation in XWLC-05 and H157 cells. In contrast, miR370 inhibitor over-expression increased the EGFR and HIF-1α expression as well as the ERK1/2 and AKT phosphorylation in XWLC-05 and H157 cells. Moreover, miR-370 over-expression significantly reduced the levels of EGFR and CD31 expression and inhibited the growth and lung metastasis of xenograft NSCLC tumors in mice. Our study indicates that miR-370 may bind to the 3′UTR of EGFR to inhibit EGFR expression and the growth, angiogenesis and metastasis of non-small cell lung cancer by down-regulating the ERK1/2 and AKT signaling.
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影响因子：
4.2
作者：
Sadeghi N;Gerber DE
通讯作者：
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影响因子：
--
作者：
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通讯作者：
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作者：
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影响因子：
254.7
作者：
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通讯作者：
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影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z