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Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro. We also found that IFITM2 expression was in part induced by insulin-like growth factor (IGF) 1 via IGF1 receptor/signal transducer and activator of transcription 3 signaling. Furthermore, IFITM2 regulated interleukin-6 expression and secretion, which in turn increased IFITM2 expression. Silencing of IFITM2 expression suppressed tumor growth and lung metastasis in vivo. These results suggest that IFITM2 is a novel prognostic biomarker and regulator of GC progression.

// Na Huang 1 , Zhenzhen Wu 1 , Li Lin 1 , Minyu Zhou 1 , Lin Wang 1 , Huanrong Ma 1 , Jianling Xia 1 , Jianping Bin 2 , Yulin Liao 2 and Wangjun Liao 1 1 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China Correspondence to: Wangjun Liao, email: // Keywords : gastric cancer; miR-338-3p; ZEB2; MACC1; epithelial-mesenchymal transition Received : December 14, 2014 Accepted : March 26, 2015 Published : April 14, 2015 Abstract MicroRNAs (miRNAs) are involved in the epithelial-mesenchymal transition (EMT) process and are associated with metastasis in gastric cancer (GC). MiR-338-3p has been reported to be aberrantly expressed in GC. In the present study, we show that miR-338-3p inhibited the migration and invasion of GC cells in vitro . Knocking down miR-338-3p in GC cells led to mesenchymal-like changes. MiR-338-3p influenced the expression of the EMT-associated proteins by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal markers, N-cadherin, fibronectin, and vimentin. In terms of mechanism, miR-338-3p directly targeted zinc finger E-box-binding protein 2 (ZEB2) and metastasis-associated in colon cancer-1 (MACC1). MiR-338-3p repressed the Met/Akt pathway after MACC1 inhibition. Reintroduction of ZEB2 and MACC1 reversed miR-338-3p-induced EMT suppression. Consistently, inverse correlations were also observed between the expression of miR-338-3p and ZEB2 or MACC1 in human GC tissue samples. In conclusion, miR-338-3p inhibited the EMT progression in GC cells by targeting ZEB2 and MACC1/Met/Akt signaling.

e17050 Background: Flotillin microdomains, essential part of plain lipid raft domains in cell membranes, have been demonstrated to participate in several intracellular signal pathways. Recent studi...

e15054 Background: Cancer cells mainly metabolize by glycolysis (the Warburg effect) and are better adapted to resist metabolic stress. Metastasis-associated in colon cancer-1 (MACC1) is an oncogen...

4042 Background: Metastasis-associated in colon cancer-1 (MACC1), a new oncogene predominantly expressed in several solid tumors including gastric cancer (GC), is associated with cancer lymph node ...

e15052 Background: Vasculogenic mimicry (VM) as a blood supplyment pattern is strongly associated with tumor progression. In a previous study, metastasis-associated in colon cancer-1 (MACC1) upregu...

e22010 Background: AberrantmicroRNAs (miRNAs) expression is involved in carcinogensis and tumor progression in gastric cancer (GC). Recently, microRNA-338-3p (miR-338-3p) has been proved to down-regulate in GC patients with deeper local invasion and advanced TNM stage. However, the underlying mechanism has not been well explored. Epithelial-mesenchymal transition (EMT) is well-known as a key step for tumor cell invasion and metastasis. Increasing evidence indicates that miRNAs play an important part in modulating EMT in many cancers. Here, we investigated the role and mechanism of miR-338-3p on EMT in GC. Methods: Cell migration and invasion ability were detected by wound-healing and transwell invasion assay.Western blot analysis was preformed to assess E-cadherin, N-cadherin, Fibronectin, Vimentin, c-Met, Akt and GSK-3β expression in GC cells. 3D cell culture system was carried out to observe the morphological changes in GC cells. Dual-luciferase assay was conducted to verify that miR-338-3p targeting ZE...