Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma
| Autor: | Alfred S. L. Cheng, Weiqin Yang, Qiaoyi Liang, Jun Yu, Ka Fai To, Wei Kang, Yujuan Dong, Li Zhang, Jesse Chung Sean Pang, Junhong Zhao, Yi Pan, Raymond W.M. Lung, Joanna H.M. Tong |
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| Rok vydání: | 2015 |
| Předmět: |
Yes-associated protein 1
Cancer Research Down-Regulation Mice Nude MicroRNA-15a Adenocarcinoma Biology medicine.disease_cause Resting Phase Cell Cycle Flow cytometry Mice MicroRNA-16-1 Cell Movement Stomach Neoplasms Cell Line Tumor microRNA medicine Animals Humans Genes Tumor Suppressor Adaptor Proteins Signal Transducing Cell Proliferation YAP1 Mice Inbred BALB C Gastric adenocarcinoma medicine.diagnostic_test Cell growth Research Tumor suppressor YAP-Signaling Proteins Cell cycle Phosphoproteins G1 Phase Cell Cycle Checkpoints Cell biology Gene Expression Regulation Neoplastic MicroRNAs Oncology Cancer research Molecular Medicine Ectopic expression Carcinogenesis G1 phase Transcription Factors |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| Popis: | Background 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. Methods 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. Results 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. Conclusion 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. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0323-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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