Xie Weiwei, Yu Jun, Yin Yujia, Zhang Xiaoqian, Zheng Xiaocui, Wang Xipeng
Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Oncol. 2022 Aug 10;12:876257. doi: 10.3389/fonc.2022.876257. eCollection 2022.
Octamer-binding transcription factor 4 (OCT4) is a key stem cell transcription factor involved in the development of various cancers. The role of OCT4 in ovarian cancer (OC) progression and its molecular mechanism are not fully understood.
First, immunohistochemistry (IHC) assays of ovarian benign cyst tissues, OC tissues, and omental metastatic tissues were performed to reveal OCT4 expression profiles. We knocked down OCT4 in two OC cell lines (SKOV3 and A2780) using a lentiviral vector and performed and experiments. OCT4 was knocked down to assess the proliferation, migration, and invasion of OC cells using CCK-8, colony formation, wound healing, and Transwell assays. In addition, the nude tumor mouse model was used for study. Mechanistically, we demonstrated that OCT4 influenced protein expression in the phosphoinositol 3-kinase (PI3K)/AKT/mTOR pathway and epithelial-mesenchymal transition (EMT)-related proteins by Western blotting and immunofluorescence (IF) assays. The interaction between OCT4 and p-AKT was further confirmed by coimmunoprecipitation (CoIP) assays. Importantly, AKT activation by its activator SC79 reversed the biological functions of OCT4 knockdown.
OCT4 expression was significantly upregulated in OC samples and metastatic tissues. OCT4 knockdown notably inhibited the proliferation, migration, and invasion of OC cells and . Moreover, the expression of p-PI3K, p-AKT, and p-mTOR was downregulated after OCT4 knockdown. An AKT agonist reversed the effect of OCT4 knockdown on OC cells. EMT in OC samples was enhanced by OCT4.
Our study shows that OCT4 promotes the proliferation, migration, and invasion of OC cells by participating in the PI3K/AKT/mTOR signaling axis, suggesting that it could serve as a potential therapeutic target for OC patients.
八聚体结合转录因子4（OCT4）是一种关键的干细胞转录因子，参与多种癌症的发生发展。OCT4在卵巢癌（OC）进展中的作用及其分子机制尚未完全明确。
首先，对卵巢良性囊肿组织、OC组织和网膜转移组织进行免疫组织化学（IHC）检测，以揭示OCT4的表达谱。我们使用慢病毒载体在两种OC细胞系（SKOV3和A2780）中敲低OCT4，并进行了CCK-8、集落形成、伤口愈合和Transwell实验，以评估敲低OCT4后OC细胞的增殖、迁移和侵袭能力。此外，利用裸鼠肿瘤模型进行研究。从机制上看，我们通过蛋白质免疫印迹法和免疫荧光（IF）检测证明，OCT4影响磷酸肌醇3激酶（PI3K）/AKT/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路中的蛋白表达以及上皮-间质转化（EMT）相关蛋白的表达。通过免疫共沉淀（CoIP）实验进一步证实了OCT4与磷酸化AKT（p-AKT）之间的相互作用。重要的是，其激活剂SC79激活AKT可逆转敲低OCT4的生物学功能。
OCT4在OC样本和转移组织中的表达显著上调。敲低OCT4显著抑制了OC细胞的增殖、迁移和侵袭。此外，敲低OCT4后，p-PI3K、p-AKT和p-mTOR的表达下调。AKT激动剂可逆转敲低OCT4对OC细胞的影响。OCT4增强了OC样本中的EMT。
我们的研究表明，OCT4通过参与PI3K/AKT/mTOR信号轴促进OC细胞的增殖、迁移和侵袭，提示它可能成为OC患者潜在的治疗靶点。
