Stathmin1 Plays Oncogenic Role and Is a Target of MicroRNA-223 in Gastric Cancer

Abstract

Stathmin1 (STMN1) is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age ( p = 0.043), T stage ( p = 0.004) and lymph node metastasis ( p = 0.046). Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis ( p = 0.01). STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation ( p<0.001), reduced monolayer colony formation ( p<0.001), inhibited cell invasion and migration ability ( p<0.001) and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo ( p<0. 01). We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.