Background and aims microRNAs (miRNAs) have been reported to regulate proliferation and migration by down-regulating the expression of target genes. The aims of this study were to investigate whether miR-4316 inhibited proliferation and migration by downregulating vascular endothelial growth factor A (VEGF-A) and its clinical significance in gastric cancer (GC). Methods The clinical tissues of the GC patients for miR-4316 and VEGF-A were detected by qRT-PCR. The protein levels of VEGF-A and c-Met were determined by western blotting. Cell Proliferation, migration, and colony forming assays were conducted to show whether miR-4316 affects proliferation by CCK-8, migration by transwell, wound healing and colony formation assays. The bioinformatic methods and luciferase reporter assay were applied to detect the relationship between miRNA and VEGF-A on its targeting 3-untranslated regions (3-UTRs). CCK-8, colony formation, wound healing, and transwell assay were performed to explore the function of miR-4316. Results The results of qRT-PCR indicated that miR-4316 expression level was significantly downregulated in human GC tissues and GC cell lines compared with their control. miR-4316 inhibited proliferation, migration and colony formation in GC cell lines by reducing VEGF-A. And western blot results indicated that miR-4316 significantly inhibited GC through repressing VEGF-A and c-Met. The investigation of Luciferase assay indicated that VEGF-A is a direct target gene of miR-4316. Conclusions miR-4316 suppressed proliferation and migration of GC through the VEGF-A gene. MiR-4316 acts as a tumor suppressor by targeting VEGF-A and this indicated that MiR-4316 might be a potential therapeutic target for GC.

中文翻译：

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MicroRNA-4316 通过直接靶向 VEGF-A 抑制胃癌的增殖和迁移。

背景和目的 据报道，microRNAs (miRNAs) 通过下调靶基因的表达来调节增殖和迁移。本研究的目的是探讨 miR-4316 是否通过下调血管内皮生长因子 A (VEGF-A) 抑制增殖和迁移及其在胃癌 (GC) 中的临床意义。方法采用qRT-PCR方法检测胃癌患者临床组织中miR-4316和VEGF-A。通过蛋白质印迹测定 VEGF-A 和 c-Met 的蛋白质水平。进行细胞增殖、迁移和集落形成测定以显示 miR-4316 是否影响 CCK-8 的增殖、transwell 的迁移、伤口愈合和集落形成测定。应用生物信息学方法和荧光素酶报告基因分析检测miRNA和VEGF-A在其靶向3-非翻译区（3-UTRs）上的关系。进行CCK-8、集落形成、伤口愈合和transwell测定以探索miR-4316的功能。结果qRT-PCR结果表明，与对照相比，miR-4316在人GC组织和GC细胞系中的表达水平显着下调。miR-4316 通过减少 VEGF-A 抑制 GC 细胞系中的增殖、迁移和集落形成。Western印迹结果表明miR-4316通过抑制VEGF-A和c-Met显着抑制GC。萤光素酶检测表明VEGF-A是miR-4316的直接靶基因。结论 miR-4316 通过 VEGF-A 基因抑制 GC 的增殖和迁移。