Abstract
Background and aimsmicroRNAs (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).MethodsThe 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.ResultsThe 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.ConclusionsmiR-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.
Highlights
Background and aimsmicroRNAs have been reported to regulate proliferation and migration by downregulating the expression of target genes
The expression of miR‐4316 is downregulated in clinical specimens and GC cell lines The expression level of miR-4316 in gastric cancer tissues and their adjacent normal tissues were determined by Quantitative reverse transcription PCR (qRT-PCR)
The expression level of miR-4316 in three human gastric cell lines SGC-7901, MGC-803 and BGC-823 were significantly downregulated compared with normal epithelial cell line GES-1as shown in Fig. 1a, b
Summary
Background and aimsmicroRNAs (miRNAs) have been reported to regulate proliferation and migration by downregulating the expression of target genes. The aims of this study were to investigate whether miR-4316 inhibited pro‐ liferation and migration by downregulating vascular endothelial growth factor A (VEGF-A) and its clinical significance in gastric cancer (GC). It was reported that about 90% of cancer deaths are caused by developed primary metastatic tumors such as gastric adenocarcinoma [3]. There are numerous stimulatory and inhibitory factors which play a role important in cancer angiogenesis for growth and metastasis of gastric cancers [5]. Along with studies of the tumor cell signal pathways, targeted medicine has become a promising strategy for the treatment of GC. The angiogenesis process plays a critical role in the growth and metastasis of the tumors [8]
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