microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1.
microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1.
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microRNA-9通过靶向Cyclin D1和Ets1抑制胃癌细胞的增殖、侵袭和转移
DOI：
10.1371/journal.pone.0055719
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tong Q
中科院分区：
文献类型：
--
作者：
Zheng L;Qi T;Yang D;Qi M;Li D;Xiang X;Huang K;Tong Q
最近的证据表明，改变microRNA-9（miR-9）的表达与胃癌的进展有关。然而，miR-9在胃癌增殖、侵袭和转移中的确切作用及其机制尚不清楚。本研究发现miR-9在胃癌组织和细胞系中表达下调，并与cyclin D1和v-ets成红细胞增多症病毒E26癌基因同源物1（Ets 1）的表达呈负相关。生物信息学分析显示，miR-9的结合位点位于cyclin D1和Ets 1 mRNA的3′-非翻译区（3′-UTR）。在培养的胃癌细胞系SGC-7901和AGS中，miR-9的异位表达或敲低导致cyclin D1、Ets 1及其下游靶点磷酸化视网膜母细胞瘤和基质金属蛋白酶9的表达相应地改变。在荧光素酶报告系统中，miR-9直接靶向细胞周期蛋白D1和Ets 1的3′-UTR，这些作用通过突变miR-9结合位点而消除。miR-9过表达可抑制SGC-7901和AGS细胞的增殖、侵袭和转移。通过瞬时转染恢复miR-9介导的细胞周期蛋白D1和Ets 1的下调，挽救了癌细胞的增殖、迁移和侵袭的减少。此外，抗miR-9抑制剂可促进胃癌细胞的增殖、迁移和侵袭，而敲低cyclin D1或Ets 1可部分模拟miR-9过表达的作用。提示miR-9通过3′-UTR结合位点抑制cyclin D1和Ets 1的表达，从而抑制胃癌的增殖、侵袭和转移。
Recent evidence shows that altered microRNA-9 (miR-9) expression is implicated in the progression of gastric cancer. However, the exact roles and underlying mechanisms of miR-9 in the proliferation, invasion and metastasis of gastric cancer still remain unknown. In this study, miR-9 was found to be down-regulated and inversely correlated with the expression of cyclin D1 and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) in gastric cancer tissues and cell lines. Bioinformatics analysis revealed the putative miR-9 binding sites in the 3′-untranslated regions (3′-UTR) of cyclin D1 and Ets1 mRNA. Ectopic expression or knockdown of miR-9 resulted in responsively altered expression of cyclin D1, Ets1 and their downstream targets phosphorylated retinoblastoma and matrix metalloproteinase 9 in cultured gastric cancer cell lines SGC-7901 and AGS. In the luciferase reporter system, miR-9 directly targeted the 3′-UTR of cyclin D1 and Ets1, and these effects were abolished by mutating the miR-9 binding sites. Over-expression of miR-9 suppressed the proliferation, invasion, and metastasis of SGC-7901 and AGS cells in vitro and in vivo. Restoration of miR-9-mediated down-regulation of cyclin D1 and Ets1 by transient transfection, rescued the cancer cells from decrease in proliferation, migration and invasion. Furthermore, anti-miR-9 inhibitor promoted the proliferation, migration and invasion of gastric cancer cells, while knocking down of cyclin D1 or Ets1 partially phenocopied the effects of miR-9 over-expression. These data indicate that miR-9 suppresses the expression of cyclin D1 and Ets1 via the binding sites in their 3′-UTR, thus inhibiting the proliferation, invasion and metastasis of gastric cancer.
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靶向转录起始位点的小 RNA 通过干扰人类癌细胞中的转录起始来诱导乙酰肝素酶沉默
影响因子：
3.7
作者：
Jiang G;Zheng L;Pu J;Mei H;Zhao J;Huang K;Zeng F;Tong Q
通讯作者：
Tong Q
DOI：
10.1111/j.1750-3639.2008.00184.x
发表时间：
2009-07
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
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作者：
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通讯作者：
Rosenfeld N
影响因子：
11.2
作者：
Hsu PY;Deatherage DE;Rodriguez BA;Liyanarachchi S;Weng YI;Zuo T;Liu J;Cheng AS;Huang TH
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DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
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通讯作者：
Rossi, John J.
影响因子：
8
作者：
Hildebrandt, M. A. T.;Gu, J.;Wu, X.
通讯作者：
Wu, X.