背景:由于缺乏早期症状,卵巢癌是最常见的妇科恶性肿瘤之一,早期诊断和有限筛查。因此,了解卵巢癌发生和发展的分子机制,确定卵巢癌的早期诊断和临床治疗的基础生物标志物是十分必要的。
方法:使用Kaplan-Meier生存分析分析FBXO28与卵巢癌预后之间的关系。从癌症基因组图谱(TCGA)获得正常卵巢组织和卵巢肿瘤组织之间FBXO28mRNA表达的差异,和基因型-组织表达(GTEx)队列。免疫组化法检测FBXO28蛋白在卵巢癌组织和正常卵巢组织中的表达。使用蛋白质印迹法测定卵巢癌细胞中FBXO28的表达水平。CCK-8,菌落形成,进行Transwell迁移和侵袭测定以评估细胞增殖和运动性。
结果:我们发现,在卵巢癌患者中,较高的FBXO28表达水平与不良预后相关。对TCGA和GTEx队列的分析表明,正常卵巢组织样品中的FBXO28mRNA水平低于卵巢癌组织样品。与正常卵巢组织或细胞系相比,FBXO28在卵巢肿瘤组织或肿瘤细胞中表达较年夜。FBXO28的上调促进了生存能力,扩散,卵巢癌细胞的迁移和侵袭。最后,我们证明FBXO28激活了卵巢癌中TGF-beta1/Smad2/3信号通路。
结论:结论:FBXO28通过上调卵巢癌中TGF-β1/Smad2/3信号通路增强致癌功能.
BACKGROUND: Ovarian cancer is one of the most common gynecological malignancies due to the lack of early symptoms, early diagnosis and limited screening. Therefore, it is necessary to understand the molecular mechanism underlying the occurrence and progression of ovarian cancer and to identify a basic biomarker for the early diagnosis and clinical treatment of ovarian cancer.
METHODS: The association between FBXO28 and ovarian cancer prognosis was analyzed using Kaplan‒Meier survival analysis. The difference in
FBXO28 mRNA expression between normal ovarian tissues and ovarian tumor tissues was obtained from The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) cohorts. The expression levels of the
FBXO28 protein in ovarian cancer tissues and normal ovarian tissues were measured via immunohistochemical staining. Western blotting was used to determine the level of
FBXO28 expression in ovarian cancer cells. The CCK-8, the colony formation, Transwell migration and invasion assays were performed to evaluate cell proliferation and motility.
RESULTS: We found that a higher expression level of
FBXO28 was associated with poor prognosis in ovarian cancer patients. Analysis of the TCGA and GTEx cohorts showed that the FBXO28 mRNA level was lower in normal ovarian tissue samples than in ovarian cancer tissue samples. Compared with that in normal ovarian tissues or cell lines, the expression of FBXO28 was greater in ovarian tumor tissues or tumor cells. The upregulation of FBXO28 promoted the viability, proliferation, migration and invasion of ovarian cancer cells. Finally, we demonstrated that
FBXO28 activated the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer.
CONCLUSIONS: In conclusion, FBXO28 enhanced oncogenic function via upregulation of the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer.