Abstract
BackgroundGastric cancer (GC) is a common cause of cancer-related mortality worldwide, and microRNAs (miRNAs) have been shown to play an important role in GC development. This study aims to explore the effect of microRNA-93-5p (miR-93-5p) on the epithelial-mesenchymal transition (EMT) in GC, via AHNAK and the Wnt signaling pathway.MethodsMicroarray-based gene expression analysis was performed to identify GC-related differentially expressed miRNAs and genes. Then the expression of the miR-93-5p was examined in GC tissues and GC cell lines. The targeting relationship between miR-93-5p and AHNAK was verified by a dual luciferase reporter gene assay. In an attempt to ascertain the contributory role of miR-93-5p in GC, miR-93-5p mimic or inhibitor, as well as an AHNAK overexpression vector, were introduced to HGC-27 cells. HGC-27 cell migration and invasive ability, and EMT were assayed using Transwell assay and western blot analysis. Regulation of the Wnt signaling pathway was also assessed using TOP/FOP flash luciferase assay.ResultsmiR-93-5p was highly expressed in GC tissue samples and cells. Notably, miR-93-5p could target and negatively regulate AHNAK. Down-regulation of miR-93-5p or overexpression of AHNAK could suppress the migration and invasion abilities, in addition to EMT in GC cells via inactivation of the Wnt signaling pathway.ConclusionTaken together, downregulation of miR-93-5p attenuated GC development via the Wnt signaling pathway by targeting AHNAK. These findings provide an enhanced understanding of miR-93-5p as a therapeutic target for GC treatment.
Highlights
Gastric cancer (GC) is a common cause of cancer-related mortality worldwide, and microRNAs have been shown to play an important role in GC development
epithelial-mesenchymal transition (EMT) is a process in which adherent epithelial cells are converted into migratory cells, which have been involved in the initiation of tumor metastasis [20]
The data obtained in our study revealed that overexpressed miR-93-5p promotes the EMT in GC through the activation of the Wnt signaling pathway via down-regulating AHNAK expression (Fig. 7)
Summary
Gastric cancer (GC) is a common cause of cancer-related mortality worldwide, and microRNAs (miRNAs) have been shown to play an important role in GC development. GC presents as the second most commonly diagnosed cancer and the second leading cause in relation to cancer mortality in China [2]. Shen et al Cancer Cell Int (2020) 20:76 stage GC, which presents with extensive invasion and metastasis, is still poor [3]. EMT is a critical event in the malignancy of cancer cells and leads to invasion and metastasis of multiple cancer cells [4]. In the process of the metastasis and invasion of GC cells, epithelial factors, such as E-cadherin are absent, while the expression of mesenchymal markers, including Snail, N-cadherin and β-catenin is elevated [6]. It is necessary to have a better understanding of the molecular mechanisms of the EMT in GC progression
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