期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 9, 页码 15027-15037出版社
WILEY
DOI: 10.1002/jcb.28764
关键词
gastric cancer; migration; miR-188-5p; proliferation; phosphatase and tensin homolog; Sal-like protein 4
资金
- China Postdoctoral Science Foundation [2017M611740]
- Jiangsu province postdoctoral research funding scheme [1701027A]
- Jiangsu province social development key research and development plan [BE2017694]
- National Natural Science Foundation of China [81302119, 81772641]
MicroRNAs (miRNAs) play pivotal roles in modulating key biological processes in gastric cancer (GC). As a newly identified miRNA, the function and potential mechanism of miR-188-5p in GC has not been thoroughly elucidated. Here, quantitative real-time polymerase chain reaction detection showed abnormally higher expression of miR-188-5p in GC cells and tissues. Gain-of-function analysis in vitro showed that miR-188-5p promoted GC cell proliferation and migration, while loss-of-function studies showed the reverse. Targetscan has predicted that phosphatase and tensin homolog (PTEN) was a potential target gene of miR-188-5p. miR-188-5p suppressed PTEN messenger RNA and protein expression and activated downstream AKT/mTOR signaling in GC cells, but luciferase reporter analysis showed that PTEN was not regulated by miR-188-5p via the 3 ' untranslated region. Furthermore, we observed that miR-188-5p overexpression promoted Sal-like protein 4 (SALL4) protein expression, cellular nuclear translocation, and transcription. Knockdown of SALL4 eliminated the effect of miR-188-5p in GC cells as well as suppression of PTEN. Taken together, our results demonstrate that miR-188-5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4. We conclude that miR-188-5p acts as an oncomiRNA in GC and may be a promising therapeutic target for GC.
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