Down-regulation of miR-326 is associated with poor prognosis and promotes growth and metastasis by targeting FSCN1 in gastric cancer

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Abstract
Background: MicroRNAs (miRNAs) have been documented as playing important roles in diverse biological processes including tumorigenesis. However, the function and mechanism of miR-326 in gastric cancer are still unknown. The aim of this study is to identify the role of miR-326 in gastric cancer and clarify the regulation of Fascin1 (FSCN1) by miR-326. Methods: The expression levels of miR-326 were detected in gastric cancer samples and cell lines by real-time PCR. The clinical and prognostic significance of miR-326 in gastric cancer patients were analyzed. Furthermore, the function of miR-326 on tumor cell growth and mobility were explored through MTT, colony formation, Transwell migration and invasion assays in vitro. A miR-326 target was confirmed using luciferase reporter assays, real-time PCR and Western blot. Results: Our study showed that miR-326 expression was decreased in gastric cancer tissues and cell lines, and low expression of miR-326 was associated to clinical stage, tumor depth, lymph node metastasis and distant metastasis. In survival analysis, low expression of miR-326 was a poor independent prognostic factor for gastric cancer patients. Gain-of-function and loss-of-function studies showed that miR-326 served as a tumor suppressor regulating gastric cancer cells growth, migration and invasion. Furthermore, we identified FSCN1 as the functional target of miR-326 by directly targeting the 3′-UTR of FSCN1. Conclusions: Our study demonstrated that miR-326 overexpression was a poor prognostic marker for gastric cancer patients, and miR-326 served as a tumor suppressor in gastric cancer via directly regulating FSCN1.

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