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BACKGROUND: DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer. METHODS: The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation. RESULTS: DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus. CONCLUSIONS: Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.
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[This corrects the article DOI: 10.3389/fonc.2021.629974.].
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The emergence and recurrence of ovarian cancer are associated with ovarian cancer stem cells. For cancer treatment, gene delivery of microbubbles (MB)-mediated microRNA (miRNA) is considered as a promising approach. In this study, our aim is to investigate the effects of MB-mediated let-7b-5p inhibitor on the proliferation and stemness characteristics of ovarian cancer (OVCA) cells. Let-7b-5p inhibitor mediated by MB was prepared (termed MB-let-7b-5p inhibitor), and the effects of MB-let-7b-5p inhibitor and let-7b-5p inhibitor on OVCA cell viability, proliferation and stemness characteristics were investigated. We found that MB-let-7b-5p inhibitor presented a higher transfection efficiency than let-7b-5p inhibitor alone. The inhibitory effect of MB-let-7b-5p inhibitor on OVCA cells was more significant than let-7b-5p inhibitor. Let-7b-5p targeted DEAD (Asp-Glu-Ala-Asp)-box helicase 19A (DDX19A), which was downregulated in OVCA cells. The downregulation of DDX19A reversed the inhibitory effects of MB-let-7b-5p inhibitor on OVCA cells. To sum up, we found that MB-let-7b-5p suppressed OVCA cell malignant behaviors by targeting DDX19A.
Asunto(s)
Proliferación Celular/genética , ARN Helicasas DEAD-box/genética , MicroARNs/genética , Proteínas de Transporte Nucleocitoplasmático/genética , Neoplasias Ováricas , Adulto , Anciano , Línea Celular Tumoral , ARN Helicasas DEAD-box/metabolismo , Femenino , Silenciador del Gen , Humanos , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Adulto JovenRESUMEN
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.