miR-632 promotes gastric cancer progression by accelerating angiogenesis in a TFF1-dependent manner

Abstract

BackgroundGastric cancer (GC) is a common malignant disease worldwide. Aberrant miRNAs expression contributes to malignant cells behaviour, and in preclinical research, miRNA targeting has shown potential for improving GC therapy. Our present study demonstrated that miR-632 promotes GC progression in a trefoil factor 1 (TFF1)-dependent manner.MethodsWe collected GC tissues and serum samples to detect miR-632 expression using real-time PCR. A dual-luciferase reporter assay was used to identify whether miR-632 directly regulates TFF1 expression. Tube formation and endothelial cell recruitment assays were performed with or without miR-632 treatment. Western blot and in situ hybridization assays were performed to detect angiogenesis and endothelial recruitment markers that are affected by miR-632.ResultsOur results showed that miR-632 is highly expressed in GC tissue and serum and negatively associated with TFF1 in GC. miR-632 improves tube formation and endothelial cell recruitment by negatively regulating TFF1 in GC cells. Recombinant TFF1 reversed miR-632-mediated angiogenesis. TFF1 is a target gene of miR-632.ConclusionsOur study demonstrated that miR-632 promotes GC progression by accelerating angiogenesis in a TFF1-dependent manner. Targeting of miR-632 may be a potential therapeutic approach for GC patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5247-z) contains supplementary material, which is available to authorized users.

Angiogenesis-related non-coding RNAs and gastrointestinal cancer

“…The expression of TFF1 is high in the normal human stomach, where it acts to preserve gastric epithelial function and structure. 178 Shi et al 179 investigated the effects of miR-632 and TFF1 on angiogenesis in GC using serum samples and GC tissues to measure the expression of miR-632 with real-time PCR. A dual-luciferase re-porter assay was performed to examine how miR-632 controlled the TFF1 expression.…”

“…miR-632 stimulated EC recruitment and tube formation, while recombinant TFF1 reversed the miR-632-induced angiogenesis. 179 RUNX1, RUNX2, and RUNX3 are members of the Runt family of transcription factors, with key roles in both normal tissue and 180 RUNX3 has a role in T cell differentiation, neurogenesis within the dorsal root ganglia, and GC tumorigenesis. 180 Lee et al 181 studied the effects of miR-495, miR-130a, and RUNX3 on angiogenesis in GC and employed bioinformatic and microarray analysis to measure the miR-130a and miR-495 expression.…”

“…Shi et al. 179 investigated the effects of miR-632 and TFF1 on angiogenesis in GC using serum samples and GC tissues to measure the expression of miR-632 with real-time PCR. A dual-luciferase reporter assay was performed to examine how miR-632 controlled the TFF1 expression.…”

“…miR-632 stimulated EC recruitment and tube formation, while recombinant TFF1 reversed the miR-632-induced angiogenesis. 179 …”

Regulation of angiogenesis by microRNAs in cancer

“…miRs may regulate TFF1 expression and secretion. Recombinant TFF1 reversed miR-632-mediated angiogenesis, and downregulated TFF1-induced tube formation and endothelial cell recruitment (79). As important regulators of gene expression, miRs have not only been implicated in various signaling pathways but also in anticancer therapy, and other biological processes.…”