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

• Published in: Molecular cancer Vol. 14; no. 1; p. 52
• Main Authors: Kang, Wei, Tong, Joanna HM, Lung, Raymond WM, Dong, Yujuan, Zhao, Junhong, Liang, Qiaoyi, Zhang, Li, Pan, Yi, Yang, Weiqin, Pang, Jesse CS, Cheng, Alfred SL, Yu, Jun, To, Ka Fai
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.02.2015; BioMed Central
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenocarcinoma - genetics; Animals; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Comparative analysis; Development and progression; Down-Regulation - genetics; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic - genetics; Genes; Genes, Tumor Suppressor - physiology; Genetic aspects; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNA; MicroRNAs - genetics; Phosphoproteins - genetics; Physiological aspects; Resting Phase, Cell Cycle - genetics; Stomach cancer; Stomach Neoplasms - genetics; Transcription Factors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-015-0323-3

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.