Cancer Management and Research (Apr 2019)
High expression of SMARCE1 predicts poor prognosis and promotes cell growth and metastasis in gastric cancer
Abstract
Hao Liu,1 Yan-Rong Zhao,2 Bo Chen,1 Zheng Ge,3 Jiang-Sheng Huang11Department of Minimally Invasive Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of General Surgery, Huaihe Hospital, Henan University, Kaifeng, Henan, People’s Republic of ChinaBackground: Gastric cancer (GC) is one of the most lethal cancers worldwide with a high risk for recurrence and metastasis. Therefore, further understanding of the metastatic mechanism and the development of treatment strategies are required. Although increasing evidence suggests that SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily E, Member 1 (SMARCE1) promotes cancer metastasis, its role in GC remains unclear.Materials and methods: GC samples (n=122) were used to investigate the association between SMARCE1 expression, patient clinicopathological features, and prognosis. The expression of SMARCE1 in GC tissues was measured using real-time polymerase chain reaction, western blotting, and immunohistochemistry. MGC-803 and AGS cells were transfected with lentivirus to upregulate or downregulate SMARCE1 expression. The roles of SMARCE1 in GC cell proliferation, migration, and invasion were determined using Cell Counting Kit-8 assay, colony formation assay, wound healing, transwell migration, and invasion assay. Nude mice models were established to observe tumorigenesis. The specific mitogen-activated protein kinase (MAPK) inhibitor U0126 was utilized to verify the involved pathway.Results: SMARCE1 was highly expressed in GC tissues and cell lines. High expression of SMARCE1 was correlated with the malignant clinicopathological characteristics of GC patients, including tumor size, depth of invasion, degree of differentiation, lymph node involvement, and TNM stage (all P<0.05). Kaplan–Meier survival analysis revealed that high SMARCE1 expression predicted poor prognosis in GC patients (P<0.01). Moreover, SMARCE1 was an independent risk factor of poor prognosis (P<0.01). Functional study revealed that overexpression of SMARCE1 markedly promoted the proliferation, migration, and invasion of GC cells in vitro and tumorigenesis in vivo. Furthermore, SMARCE1 activated the MAPK/ERK signaling pathway. U0126 significantly inhibited the SMARCE1-induced proliferation and mobility of GC cells.Conclusion: SMARCE1 promoted growth and metastasis of GC, indicating its potential usefulness as a prognostic biomarker and target for therapeutic intervention against this disease.Keywords: SMARCE1, gastric cancer, prognosis, proliferation, metastasis
