Abstract

BackgroundmiR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge.MethodsLuciferase reporter assay was conducted to verify the binding of miR-124-3p and HOXA11-AS. RT-PCR and western blot were performed to detect the expression of HOXA11-AS, miR-124-3p and ITGB3 in GC tissues and cells. Gene silence and overexpression experiments as well as cell migration and invasion assays on GC cell lines were performed to determine the regulation of molecular pathways, HOXA11-AS/miR-124-3p/ITGB3. Furthermore, the role of HOXA11-AS in GC was confirmed in mice models.ResultsWe found HOXA11-AS is up-regulated in GC tissues and can bind with miR-124-3p. Through overexpression/knockdown experiments and function tests in vitro, we demonstrated HOXA11-AS can promote ITGB3 expression by sponging miR-124-3p, consequently enhance the proliferation, migration, and invasion of GC cells. Meanwhile, we validated that HOXA11-AS promotes migration and invasion of GC cells via down-regulating miR-124-3p and up-regulating ITGB3 in vivo.ConclusionsWe demonstrated that lncRNA HOXA11-AS can increase ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Our results suggested that HOXA11-AS may reasonably serve as a promising diagnostic biomarker and a potential therapeutic target of GC.

Highlights

  • MiR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process long non-coding RNAs (lncRNAs) HOXA11-AS may act as a molecular sponge

  • The lncRNA HOXA11‐AS is up‐regulated in GC tissues and correlated with miR‐124‐3p and ITGB3 expression To investigate the function of lncRNA HOXA11-AS in gastric cancer, we first assessed the expression levels of HOXA11-AS in gastric cancer tissues and adjacent normal tissues of patients

  • The results showed that lncRNA HOXA11-AS expression of GC tissues was statistically higher than that of adjacent normal tissues (P < 0.001, Fig. 1a)

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Summary

Introduction

MiR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge. Despite the fast advancements of diagnostic and therapeutic strategies in recent years, Integrin β3 (ITGB3) can promote GC invasion and metastasis and some micro-RNAs (miRNAs) can. You et al Cancer Cell Int (2021) 21:576 regulate the expression of ITGB3. Previous studies demonstrated that miRNA-124-3p (miR-124-3p) can down-regulate ITGB3 expression and inhibit gastric cancer cell proliferation and migration [3,4,5,6]. Our previous study explored the action of miR-124-3p/ITGB3 in GC invasion and migration [7]. We revealed miR-124-3p can bound to partial complementary sites of ITGB3 mRNA and induce post-transcriptional silencing of the ITGB3 gene to inhibit gastric cancer cell proliferation and invasion. The molecular mechanisms underlying the role of miR-124-3p/ITGB3 in GC progression are still not well documented

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