Abstract
BackgroundMicroRNAs (miRNAs) are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC). Expression profiling of miRNAs in paired gastric cancer and adjacent normal gastric tissues has demonstrated that miR-4455 is down-regulated in gastric cancer tissues, but its functional role in the carcinogenesis of GC had not previously been investigated.AimsThe purpose of this study was to investigate the functional and biological mechanisms of miR-4455 in the progression of GC, in vitro.MethodsExpression of miR-4455 was compared in human GC tissue samples and paired adjacent normal tissue samples. The in vitro effects of miR-4455 expression in MGC-803 cells on their proliferation, invasion, and migration were assessed by MTT assays and 5-bromo-2′-deoxyuridine staining, matrigel-invasion analysis and wound healing assays. Bioinformatics analysis (using PicTar, target scan and miRBase target) was used to identify potential targets for miR-4455, and the luciferase reporter assay, qRT-PCR and Western-blotting analyses were used to confirm VASP as the target of miR-4455. In addition, the effects of downregulation of VASP on the activation of PI3K/AKT signaling pathway were measured using Western-blot analysis.ResultsThe expression of miR-4455 was markedly down-regulated in gastric cancer tissues vs. adjacent normal tissues, and miR-4455 expression inhibited the proliferation, invasion and migration of MGC-803 GC cells in vitro. Luciferase reporter assays revealed that miR-4455 inhibited VASP expression by targeting the 3′-UTR sequence of VASP. Furthermore, silencing of VASP markedly inhibited the activation of the PI3K/AKT signaling pathway.ConclusionOur results suggest that miR-4455 functions as a tumor suppressor in gastric cancer, by targeting VASP leading to activation of the PI3K/AKT signaling pathway and the inhibition of VASP mediated proliferation, migration and invasion of gastric cancer cells.
Highlights
MicroRNAs are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC)
Our results suggest that miR-4455 functions as a tumor suppressor in gastric cancer, by targeting vasodilator-stimulated phosphoprotein (VASP) leading to activation of the PI3K/AKT signaling pathway and the inhibition of VASP mediated proliferation, migration and invasion of gastric cancer cells
Results miR‐4455 is down regulated in GC tissues and GC cells Real-time RT-PCR analysis of extracted RNA from the human paired tissue samples revealed that the expression of miR-4455 was significantly down-regulated in gastric cancer tissues compared with adjacent-normal gastric tissues (P < 0.05) (Fig. 1a)
Summary
MicroRNAs (miRNAs) are small non-coding RNAs which play important roles in the carcinogenesis of gastric cancer (GC). Expression profiling of miRNAs in paired gastric cancer and adjacent normal gastric tissues has demonstrated that miR-4455 is down-regulated in gastric cancer tissues, but its functional role in the carcinogenesis of GC had not previously been investigated. MicroRNAs (miRNAs) are small non-coding RNAs which have important functional roles in animals by regulating post-translational gene expression. They act through binding to the three prime untranslated region (3′-UTR) of their target mRNAs. It has been reported that microRNAs participate in the carcinogenetic processes of many cancers, including regulating the development, differentiation and proliferation of cancer cells [1,2,3,4]. In the present study we aimed to identify the functional molecular target of miR-4455 and to uncover the possible regulatory pathway by which its effects are exerted
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