Effects of miR-18a on proliferation and apoptosis of gastric cancer cells by regulating RUNX1

B. Qi, Y. Dong, X.-L. Qiao

Department of Abdominal Emergency Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China. dongying0721@dmu.edu.cn

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• Oncology

OBJECTIVE: The aim of this study was to explore the effects of micro ribonucleic acid (miR)-18a on the proliferation and apoptosis of gastric cancer (GC) cells, and to elucidate the possible underlying mechanism.

PATIENTS AND METHODS: In this study, the expression of miR-18a in GC tissues and para-cancer tissues was verified by in situ hybridization (ISH) of GC tissue microarray (TMA). Meanwhile, the effect of miR-18a expression on the prognosis of GC patients was evaluated. GC AGS cell line was selected and transfected with miR-18a mimic and mimic control (NC) to up-regulate miR-18a expression in vitro. Thereafter, changes in cell proliferation, apoptosis and migration after transfection were detected by biological functional assays. Luciferase reporter gene assay was carried out to verify the target gene Runt-related transcription factor 1 (RUNX1) modulated by miR-18a. Finally, the Spearman’s grade correlation coefficient was calculated to explore the correlation between the expressions of miR-18a and RUNX1.

RESULTS: ISH results of TMA showed that overexpression of miR-18a in GC tissues was significantly associated with low survival rate of patients (p<0.001). High expression of miR-18a remarkably enhanced the proliferation, migration and invasion of GC cells (p<0.05). Besides, it has been predicted in biology that RUNX1 is one of the target genes of miR-18a. Luciferase reporter gene assay showed that Luciferase activity in cells transfected with wild-type (WT) RUNX1 3’ untranslated region (3’UTR) was significantly reduced (p<0.05). Moreover, the protein expression of RUNX1 decreased remarkably in GC cells with over-expression of miR-18a (p<0.05). All these findings indicated that the expression of miR-18a was negatively correlated with RUNX1 in GC cells (p<0.001, r=0.86).

CONCLUSIONS: MiR-18a exerts a high predictive value for the prognosis of GC patients by directly targeting the transcription factor RUNX1. All our findings may provide therapeutic candidates for GC identification.

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