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Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer.

ABSTRACT: Ovarian cancer (OC) is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Rencently, Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in ovarian cancer is still not fully understood. Here, we investigated the effects of ADARB1 on OC biology. By conducting bioinformatics analyses of several public databases, we found significantly decreased ADARB1 expression in OC cells and tissues. Moreover, RT-PCR and western blot showed lower ADARB1 expression in OVCAR3, HO8910pm and A2780 OC cells compared to human normal ovarian epithelial cell IOSE. Cell proliferation assay and clone formation assay showed that overexpression of ADARB1 (ADARB1-OE) inhibited the proliferation of tumor cells. Wound healing and transwell assay indicated that ADARB1-OE could suppress OC cell invasion and metastasis. Kaplan-Meier methods revealed that the patients with low level of ADARB1 displayed poor prognosis. TISIDB databases were further used to analyze the roles of ADARB1 in tumor-immune system interactions in OC patients. Furthermore, ADARB1-OE down-regulated the expression of phosphorylated AKT. Combination of ADARB1-OE and AKT inhibitor MK2206 exerted stronger cell growth inhibition. Thus, our investigation demonstrated that low levels of ADARB1 might be a potential target in the tumorigenesis and prognostic evaluation of OC patients.

SUBMITTER: Zhu W

PROVIDER: S-EPMC8733684 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aim:The aim of this study was to explore the expression of peroxiredoxin1 (PRDX1) in epithelial ovarian cancer, analyze the relationship between PRDX1 and clinicopathologic parameters of patients with ovarian cancer, including their prognosis, and describe changes and the mechanisms involved in malignant biologic behavior of ovarian cancer cells when PRDX1 expression is inhibited. Methods:The expression of PRDX1 was detected immunohistochemically in 15 samples of normal ovarian tissue, 21 benign, 11 borderline, and 101 malignant epithelial ovarian tumors. Changes in ovarian cancer cell proliferation, invasion, and metastasis before and after inhibiting PRDX1 expression were assessed by cell function assay. Additionally, gene set enrichment analysis (GSEA) of PRDX1 was performed by the Cancer Genome Atlas database. A protein- protein interaction network was then constructed and a pathway function analysis of the genes in the network was conducted. Results:PRDX1 expression was mainly localized to the cytoplasm, as well as the nucleus of cells. The expression rate of PRDX1 in epithelial ovarian malignant tissues (96.04%) was significantly higher than that in borderline (72.72%) and benign (57.14%) epithelial ovarian tumors, and normal ovarian tissue (20%; all P<0.05). Cox multivariate regression analysis indicated that advanced clinical stage, low tissue differentiation, and high expression of PRDX1 were independent risk factors affecting the prognosis of epithelial ovarian cancer (all P<0.05). Cell function assay verified that the decreased expression of PRDX1 inhibited ovarian cancer cell proliferation, invasion, and metastasis. GSEA analysis indicated that PRDX1 was significantly related to the Wnt signaling pathway. Western blot analysis confirmed that PRDX1 could regulate the expression of ?-catenin in the Wnt pathway. Conclusion:Decreased expression of PRDX1 can attenuate cell proliferation, invasion, and metastasis of ovarian cancer cells. The expression of PRDX1 is related to the prognosis of patients with ovarian cancer and can therefore be used as a biomarker.

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Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer.

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