DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

Yanhui Jiang,Yongliang Li,Shangqiu Chen,Changqing Liu,Hua Yang,Yutao Wei,Huanhuan He,Jiahui Shen,Feng Wang,Jihong Liu,Yong Chen,Baibin Wang,Hanjie Li,Famin Zeng

doi:10.3389/fonc.2021.629974

Abstract

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

Highlights

Cervical cancer is one of the most common gynecological malignancies and the second leading cause of cancer-related deaths among women worldwide [1]
The diagnosis of CSCC was confirmed by pathologists, and the study was approved by Abbreviations: TCGA, The Cancer Genome Atlas; GEO, Gene Expression Omnibus; CSCC, cervical squamous cell carcinoma; ATCC, American Type Culture Collection; NAC, N-acetylcysteine; DDX19A, DEAD-box helicase 19A; NOX1, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1; ROS, reactive oxygen species
In-depth analysis of TCGA database showed that DDX19A expression was higher in CSCC with distant metastasis (M1) than that in specimens without metastasis (M0) (Figure 1D)

Summary

Introduction

Cervical cancer is one of the most common gynecological malignancies and the second leading cause of cancer-related deaths among women worldwide [1]. Thanks to advances in surgery, chemotherapy, radiotherapy, and immunotherapy, the 5-year survival rate for patients with cervical cancer has increased to 80%. Metastasis is the primary cause of death in patients with cervical cancer [3, 4], and cervical squamous cell carcinoma (CSCC) is the most common pathologic type of cervical cancer, accounting for ∼80% of all cases [5]. Recent studies have revealed that many DEAD-box proteins were abnormally expressed and play pivotal roles in cancer metastasis [11,12,13,14]. The expression and function of DEAD-box proteins in CSCC remain unknown

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Results

Conclusion