MiR-99a suppresses cell migration and invasion by regulating IGF1R in gastric cancer

摘要

OBJECTIVE: Gastric cancer is a common kind of gastrointestinal malignancies. Increasing evidence indicates dysregulation of microRNA-99a (miR-99a) in gastric cancer, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. The purpose of this study is to explore how miR-99a worked in gastric cancer on migration and invasion. PATIENTS AND METHODS: The mRNA and protein levels of miR-99a and insulin-like growth factor 1 receptor (IGF1R) in gastric cancer were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Transwell assay was employed to analyze the migratory and invasive capacities. The Dual-Luciferase reporter assay was performed to confirm miR-99a mediated the expression of IGF1R by directly targeting its mRNA 3’-untranslated regions (3’-UTR) in gastric cancer cells. RESULTS: MiR-99a was discovered to be significantly downregulated while IGF1R was upregulated in gastric cancer tissues and cell lines. The expression of miR-99a had a negative correlation with the IGF1R expression in gastric cancer tissues. Moreover, miR-99a was low expressed in gastric cancer cells HGC-27 and MGC-803 compared to the normal cell line. MiR-99a suppressed the migration and invasion through directly binding to the 3’-UTR of IGF1R mRNA in HGC-27 cells. In addition, IGF1R could reverse partial roles of miR-99a on migration and invasion in gastric cancer. CONCLUSIONS: MiR-99a inhibited the migratory and invasive abilities by regulating the expression of IGF1R. MiR-99a was downregulated while IGF1R was upregulated in gastric cancer cell lines. The newly identified miR-99a/IGF1R axis provides novel insight into the pathogenesis of gastric cancer.