MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.
MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.
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MiR-646通过靶向FOXK1抑制胃癌细胞增殖和EMT诱导的转移
DOI：
10.1038/bjc.2017.181
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发表时间：
2017-08-08
影响因子：
8.8
通讯作者：
Wang JD
中科院分区：
文献类型：
--
作者：
Zhang P;Tang WM;Zhang H;Li YQ;Peng Y;Wang J;Liu GN;Huang XT;Zhao JJ;Li G;Li AM;Bai Y;Chen Y;Ren YX;Li GX;Wang YD;Liu SD;Wang JD
背景：MiR-646已被报道在人类癌症中异常表达。然而，miR-646在胃癌（GC）中作用的潜在分子机制尚未被研究。方法：采用EdU法、平板集落形成法和基质侵袭法评价miR-646在GC中的体外功能。Real-time PCR或western blotting检测miR-646和FOXK1的表达。在裸鼠体内进行肿瘤的生长和转移。结果：与邻近正常组织相比，GC组织中MiR-646表达下调。miR-646低表达与恶性进展相关。短暂转染miR-646抑制GC细胞的生长和迁移。此外，miR-646影响上皮-间质转化（EMT）相关蛋白的表达。TGF-β1处理显著抑制miR-646的表达，该microRNA的过表达抵消了TGF-β1诱导的EMT表型的影响。就其潜在机制而言，miR-646直接靶向FOXK1。在体内，它抑制foxk1介导的增殖和emt诱导的转移。同样，在人GC组织样本中miR-646和FOXK1的表达之间也观察到负相关。此外，miR-646在FOXK1之后调控Akt/mTOR信号传导。结论：miR-646通过靶向FOXK1抑制GC细胞增殖和EMT进展。
Background:MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated.Methods:In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice.Results:MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial–mesenchymal transition (EMT)-associated proteins. TGF-β1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-β1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1.Conclusions:miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
C-JUN对FOXK1的直接调节促进了胃癌细胞中的增殖，侵袭和转移。
影响因子：
9
作者：
Peng Y;Zhang P;Huang X;Yan Q;Wu M;Xie R;Wu Y;Zhang M;Nan Q;Zhao J;Li A;Xiong J;Ren Y;Bai Y;Chen Y;Liu S;Wang J
通讯作者：
Wang J
miR-340和ZEB1负反馈环调节TGF-β介导的乳腺癌进展
影响因子：
--
作者：
Hou LK;Yu Y;Xie YG;Wang J;Mao JF;Zhang B;Wang X;Cao XC
通讯作者：
Cao XC
影响因子：
--
作者：
Dong P;Ihira K;Xiong Y;Watari H;Hanley SJ;Yamada T;Hosaka M;Kudo M;Yue J;Sakuragi N
通讯作者：
Sakuragi N
影响因子：
24.5
作者：
Hur K;Toiyama Y;Takahashi M;Balaguer F;Nagasaka T;Koike J;Hemmi H;Koi M;Boland CR;Goel A
通讯作者：
Goel A