miR-144 suppresses cell proliferation and invasion in gastric cancer through downregulation of activating enhancer-binding protein 4

Oncol Lett. 2019 Jun;17(6):5686-5692. doi: 10.3892/ol.2019.10214. Epub 2019 Apr 4.

Abstract

Gastric cancer (GC) is the most common malignant disease and its incidence rate is increasing rapidly worldwide. The molecular mechanisms underlying GC tumorigenesis require further investigation. The expression and physiological roles of microRNA-144 (miR-144) have been investigated in numerous types of tumor. However, its biological function in GC remains largely unknown. The reverse transcription- quantitative polymerase chain reaction was used to determine the expression of miR-144 in GC cells and normal gastric epithelial cells. An miR-144 mimic was transfected into HGC-27 cells. In addition, bioinformatics analysis was performed to identify the potential targets of miR-144. Protein expression, luciferase and rescue assays were used to confirm the target of miR-144. It was identified that the expression of miR-144 was significantly downregulated in GC cells compared with in normal gastric epithelial cells. Furthermore, overexpression of miR-144 suppressed HGC-27 cell proliferation, migration and invasion. Additionally, bioinformatics analysis suggested that the activating enhancer-binding protein 4 (AP4) is a target gene of miR-144. In addition, it was determined that miR-144 suppresses the expression of AP4 by binding directly to its 3'-untranslated regions. Furthermore, restoration of AP4 partially attenuated miR-144-induced inhibition of cell proliferation, migration and invasion. Therefore, the results of the present study suggest that miR-144 serves an important role in GC progression.

Keywords: activating enhancer-binding protein 4; gastric cancer; invasion; microRNA-144; proliferation.