Table1_Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer.XLSX

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.

卵巢癌（OC）通常在晚期才被确诊，给临床治疗与患者康复带来极大挑战。近年来，腺苷脱氨酶RNA特异性B1（ADARB1）作为一种腺苷至肌苷（A-to-I）RNA编辑酶，被证实在癌症发生发展过程中发挥关键作用。然而，ADARB1在卵巢癌中的具体功能仍未完全阐明。本研究探究了ADARB1对卵巢癌生物学特性的影响。通过对多个公共数据库开展生物信息学分析，我们发现卵巢癌细胞与组织中ADARB1的表达水平显著降低。此外，逆转录PCR（RT-PCR）与蛋白质印迹（Western Blot）结果显示，相较于人正常卵巢上皮细胞IOSE，OVCAR3、HO8910pm及A2780三种卵巢癌细胞中ADARB1的表达水平显著更低。细胞增殖实验与克隆形成实验结果表明，过表达ADARB1（ADARB1-OE）可抑制肿瘤细胞的增殖能力。划痕实验与Transwell实验结果表明，ADARB1-OE能够抑制卵巢癌细胞的侵袭与转移能力。采用Kaplan-Meier法分析显示，ADARB1低表达的卵巢癌患者预后较差。本研究进一步利用TISIDB数据库，分析了ADARB1在卵巢癌患者肿瘤与免疫系统互作过程中的作用。此外，ADARB1-OE可下调磷酸化AKT的表达水平；ADARB1过表达与AKT抑制剂MK2206联合使用时，对细胞增殖的抑制作用更为显著。综上，本研究证实ADARB1低表达可能成为卵巢癌患者肿瘤发生及预后评估的潜在靶点。