Oncotarget

Research Papers:

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

Xiao-Lu Lin, Li Yang, Seng-Wang Fu, Wen-Feng Lin, Yun-Jie Gao, Hao-Yan Chen and Zhi-Zheng Ge _

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Oncotarget. 2017; 8:33586-33600. https://doi.org/10.18632/oncotarget.16829

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Abstract

Xiao-Lu Lin1,*, Li Yang1,*, Seng-Wang Fu3,*, Wen-Feng Lin1, Yun-Jie Gao1, Hao-Yan Chen2, Zhi-Zheng Ge1

1Division 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

2Division 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

3Department 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.


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