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

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

doi:10.18632/oncotarget.16829

Xiao-Lu Lin, Seng-Wang Fu + Show 5 more

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https://doi.org/10.18632/oncotarget.16829

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Journal: Oncotarget	Publication Date: Apr 4, 2017
Citations: 61	License type: cc-by

Affiliation: Shanghai Jiao Tong University

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.

Highlights

Colorectal cancer (CRC) is the third most common type of malignancy in men and the second in women worldwide, with over 1.2 million new cases recorded and about 600,000 deaths per year [1,2,3]
We demonstrated that when NADPH oxidase 4 (NOX4) expression was knocked down by Small interfering RNAs (siRNAs), cell proliferation, cell-cycle and apoptosis, migration and invasion were significantly altered in CRC cell lines HCT116 and LOVO
According to the proliferation and apoptosis pathways in GeneSet Enrichment Analysis (GSEA), we found GLI1, a well-known transcription factor involved in the growth of many human tumours [21,22,23], was active in patients with higher NOX4 expression

Summary

Introduction

Colorectal cancer (CRC) is the third most common type of malignancy in men and the second in women worldwide, with over 1.2 million new cases recorded and about 600,000 deaths per year [1,2,3]. The prognoses of CRC patients between early and advanced stages can vary from a 5-year survival rate of 93% at Stage I to 8% at Stage IV [4]. More studies are needed to explore the potential mechanism and detect effective diagnostic and prognostic biomarkers to prolong the lives of CRC patients. High level of ROS can induce cell senescence, apoptosis and death due to their cytotoxic and mutagenic potential. ROS at low level serve as regulators of cell growth, differentiation, apoptosis and gene expression [6]. Tumors always exhibit excessive and persistent elevation of ROS, and several studies have demonstrated that ROS may be associated with human carcinogenesis [7, 8]

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