MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2

• Main Authors: Yu He, Yugang Ge, Mingkun Jiang, Jundong Zhou, Dakui Luo, Hao Fan, Liang Shi, Linling Lin, Li Yang
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-06-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Mir-592; Spry2; EMT; PI3K/AKT and MAPK/ERK signaling pathways; Gastric cancer
• Online Access: https://www.karger.com/Article/FullText/490839
• ISSN: 1015-8987; 1421-9778

Background/Aims: Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Methods: Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial–mesenchymal transition (EMT) were detected with western blot. Results: The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Conclusions: Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC.