Tian Yuejun, Qi Ping, Hu Xuemei
Department of Obstetrics and Gynecology, Lanzhou University Second Hospital, Lanzhou, China.
Department of Clinical Laboratory, Lanzhou University Second Hospital, Lanzhou, China.
Front Oncol. 2020 Jun 16;10:903. doi: 10.3389/fonc.2020.00903. eCollection 2020.
Emerging studies have demonstrated that the Forkhead transcription factor FOXO3a is closely correlated with the progression of multiple tumors. Nevertheless, the biological role and prognostic value of FOXO3a have yet to be fully elucidated in cervical carcinoma. This study was designed to determine the molecular mechanism and prognosis of FOXO3a in cervical carcinoma. The protein levels of FOXO3a were detected using immunohistochemistry and Western blotting. The relationships between FOXO3a expression and clinicopathological variables were analyzed. The biological mechanism of FOXO3a in cervical carcinoma cells (HeLa and CaSki) was investigated. We also explored the effect of FOXO3a on WNT/β-catenin signaling with respect to its expression and function. The results demonstrated that decreased FOXO3a expression was related to increased tumor stage and grade, positive lymph node metastasis, and poor survival outcome in cervical carcinoma. Survival analysis revealed that the FOXO3a level is an independent prognostic factor for cervical carcinoma patients. Furthermore, the data indicated that the downregulation of FOXO3a expression promotes cell invasion and migration, while FOXO3a overexpression exhibited the opposite effects on cervical carcinoma. In addition, FOXO3a acted as a negative regulator of the canonical WNT/ β-catenin pathway in cervical carcinoma. Moreover, overexpression of FOXO3a also inhibited the expression of MMP2 and MMP9. These results reveal that FOXO3a, serving as a tumor suppressor gene, could suppress cell invasion and migration via the WNT/β-catenin signaling pathway and indicates a good prognosis in cervical carcinoma.
新兴研究表明，叉头转录因子FOXO3a与多种肿瘤的进展密切相关。然而，FOXO3a在宫颈癌中的生物学作用和预后价值尚未完全阐明。本研究旨在确定FOXO3a在宫颈癌中的分子机制和预后情况。采用免疫组织化学和蛋白质印迹法检测FOXO3a的蛋白水平。分析FOXO3a表达与临床病理变量之间的关系。研究FOXO3a在宫颈癌细胞（HeLa和CaSki）中的生物学机制。我们还探讨了FOXO3a对WNT/β-连环蛋白信号通路表达和功能的影响。结果表明，FOXO3a表达降低与宫颈癌的肿瘤分期增加、分级升高、淋巴结转移阳性及生存结果较差有关。生存分析显示，FOXO3a水平是宫颈癌患者的独立预后因素。此外，数据表明，FOXO3a表达下调促进细胞侵袭和迁移，而FOXO3a过表达对宫颈癌表现出相反的作用。此外，FOXO3a在宫颈癌中作为经典WNT/β-连环蛋白通路的负调节因子。而且，FOXO3a过表达还抑制MMP2和MMP9的表达。这些结果表明，FOXO3a作为一种肿瘤抑制基因，可通过WNT/β-连环蛋白信号通路抑制细胞侵袭和迁移，并提示宫颈癌预后良好。
