MiR-188-5p emerges as an oncomiRNA to promote gastric cancer cell proliferation and migration via upregulation of SALL4.

Abstract

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.