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Open Access 01-12-2015 | Research

Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma

Authors: Wei Kang, Joanna HM Tong, Raymond WM Lung, Yujuan Dong, Junhong Zhao, Qiaoyi Liang, Li Zhang, Yi Pan, Weiqin Yang, Jesse CS Pang, Alfred SL Cheng, Jun Yu, Ka Fai To

Published in: Molecular Cancer | Issue 1/2015

Abstract

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.

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Title: Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma
Authors: Wei Kang
Joanna HM Tong
Raymond WM Lung
Yujuan Dong
Junhong Zhao
Qiaoyi Liang
Li Zhang
Yi Pan
Weiqin Yang
Jesse CS Pang
Alfred SL Cheng
Jun Yu
Ka Fai To
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-015-0323-3

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Abstract

Background

Methods

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Conclusion

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