Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma.
Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma.
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DOI：
10.1186/s12943-015-0323-3
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发表时间：
2015-02-22
期刊：
影响因子：
37.3
通讯作者：
To KF
中科院分区：
文献类型：
--
作者：
Kang W;Tong JH;Lung RW;Dong Y;Zhao J;Liang Q;Zhang L;Pan Y;Yang W;Pang JC;Cheng AS;Yu J;To KF
MicroRNAs(MiRNAs)已被报道在肿瘤的发生中发挥重要作用。本研究探讨miR-15a和miR-16-1在胃腺癌中的作用。用miRNAqRT-PCR方法检测miR-15a和miR-16-1在细胞株和原发肿瘤中的表达。通过异位表达miR-15a和miR-16-1，进行细胞增殖实验、克隆形成、细胞侵袭和迁移、流式细胞仪分析和体内实验。用TargetScan对miR-15a和miR-16-1可能的靶基因进行了探索和进一步验证。我们发现与正常胃上皮相比，miR-15a和miR-16-1在GAC细胞系和原发肿瘤组织中表达下调。功能研究表明，异位表达miR-15a和miR-16-1抑制了体内细胞的增殖、单层集落形成、侵袭和迁移以及异种移植瘤的形成。此外，miR-15a和miR-16-1还诱导G0/G1期细胞周期停滞，相关细胞周期调节因子的Western印迹和qRT-PCR进一步证实了这一点。YAP1被证实为miR-15a和miR-16-1在GAC中的功能靶点。YAP1的重新表达部分阻断了miR-15a和miR-16-1对GAC细胞的抑制作用。在临床标本中，YAP1蛋白表达与miR-15a、miR-16-1表达呈负相关。结论：肿瘤抑制基因miRNAmiR-15a和miR-16-1靶向YAP1对GAC有一定的抑制作用，可能具有治疗GAC的潜力。本文的在线版本(doi：10.1186/s12943-0150323-3)包含补充材料，授权用户可以使用。
MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated. The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated. We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression. In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC. The online version of this article (doi:10.1186/s12943-015-0323-3) contains supplementary material, which is available to authorized users.
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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
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影响因子：
4.1
作者：
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