MiR-17-5p promotes cellular proliferation and invasiveness by targeting RUNX3 in gastric cancer.

BACKGROUND:Dysregulated microRNAs (miRNAs/miRs) directly modulate the biological functions of gastric cancer (GC) cells and contribute to the initiation and progression of GC. MiR-17-5p and runt-related transcription factor 3 (RUNX3) have been reported to be related to GC progression; however, the specific interaction between miR-17-5p and RUNX3 in GC require further investigation. METHODS:Western blotting, real-time PCR and immunohistochemistry were used to study the expression level of miR-17-5p and RUNX3 in gastric cancer tissues and plasma. The biological function of miR-17-5p was examined by measuring cell proliferation, apoptosis and cell invasion in vitro; the target gene of miR17-5p was identified by luciferase reporter assays, RNA Binding protein immunoprecipitation (RIP) and western blotting. In vivo animal study was conducted to confirm the role of miR-17-5p during tumorigensis of gastric cancer. RESULTS:This study showed that miR17-5p was upregulated in the plasma and tissues of patients with GC, while RUNX3 was downregulated in GC tissues. Functional experiments indicated that miR-17-5p mimics promoted the proliferation and invasion of GC via suppressing apoptosis in vitro. Furthermore, bioinformatics prediction, luciferase reporter assays, reverse transcription quantitative polymerase chain reaction assays, RIP and western blotting analysis demonstrated that RUNX3 was a direct target gene of miR-17-5p in GC. In addition, overexpression of RUNX3 suppressed the proliferation and invasiveness of GC cells. In vivo data indicated miR-17-5p agomir significantly promoted tumor growth. In contrast, miR-17-5p antagomir notably decreased tumor volume compared with control group. CONCLUSIONS:MiR-17-5p promoted the progression of GC via directly targeting RUNX3, suggesting that miR-17-5p and RUNX3 could be considered as diagnostic and therapeutic targets for patients with GC.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}