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Overexpression of NOX4 predicts poor prognosis and promotes tumor progression in human colorectal cancer

2017; Impact Journals LLC; Volume: 8; Issue: 20 Linguagem: Inglês

10.18632/oncotarget.16829

1949-2553

Xiaolu Lin, Yang Li, Sengwang Fu, Wenfeng Lin, Yun‐Jie Gao, Haoyan Chen, Zhi‐Zheng Ge,

Angiogenesis and VEGF in Cancer

// Xiao-Lu Lin 1, * , Li Yang 1, * , Seng-Wang Fu 3, * , Wen-Feng Lin 1 , Yun-Jie Gao 1 , Hao-Yan Chen 2 , Zhi-Zheng Ge 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 3 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China * These authors have contributed equally to this work Correspondence to: Zhi-Zheng Ge, email: zhizhengge@aliyun.com Hao-Yan Chen, email: chen_haoyan@126.com Keywords: colorectal carcinoma, NOX4, prognosis, proliferation, metastasis Received: December 09, 2016 Accepted: March 25, 2017 Published: April 04, 2017 ABSTRACT NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS) production, has been increasingly reported to be involved in tumorigenesis and/or tumor progression, but limited data are available regarding the role of NOX4 in colorectal carcinoma (CRC). We retrieved six independent investigations from Oncomine database and found that NOX4 is highly expressed in CRC tissues compared with corresponding normal controls. Similar results were also found in clinical specimens at both mRNA and protein levels. Immunohistochemical analysis indicated that NOX4 overexpression was highly correlated with T classification, N classification, distant metastasis, and poor prognosis of CRC patients, which was also confirmed by GSE14333 and GSE17536 datasets from the Gene Expression Omnibus. Furthermore, we demonstrated that when NOX4 expression was knocked down by siRNAs, cell proliferation, cell-cycle and apoptosis, migration and invasion were significantly altered in CRC cell lines HCT116 and LOVO. Meanwhile, NOX4 promoted cancer cell proliferation and apoptosis, migration and invasion by regulating the expression of relevant genes. By these approaches we aim to elucidate NOX4 may be a reliable prognostic factor or therapeutic target in CRC.