Lu Fangfang, Xu Hong, Wang Qi, Li Meiyi, Meng Jiahua, Kuang Yan
Department of Obstetrics and Gynecology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541000, P.R. China.
Department of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Lett. 2018 Mar;15(3):3233-3239. doi: 10.3892/ol.2017.7712. Epub 2017 Dec 28.
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which targets histone H3 lysine 27. Studies have reported that EZH2 is involved in the development of several types of tumor, including ovarian cancer. p16, a well-known cell cycle regulator, has been demonstrated to be a tumor suppressor gene in a variety of malignant cells. However, the regulatory association between EZH2 and p16 in ovarian cancer remains to be fully elucidated. The present study aimed to determine whether EZH2 is involved in the development of ovarian cancer by regulating the expression of p16. An EZH2 short hairpin RNA (shRNA) lentiviral vector was constructed and used for transducing A2780 and SKOV3 ovarian cancer cell lines. The expression levels of EZH2 and p16 in the ovarian cancer cells were detected using a reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The function of the inhibition of EZH2 in cell proliferation and migration were determined using a CCK-8 assay and Transwell assay. In addition, a nude mouse xenograft model was used to determine the function of EZH2 and p16 in the formation of ovarian cancer . The results revealed that the inhibition of EZH2 increased the expression of p16, and suppressed the proliferation and migration capabilities of ovarian cancer . The downregulated expression of EZH2 suppressed ovarian tumor formation . The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy.
zeste 同源物 2 增强子（EZH2）是一种组蛋白甲基转移酶，其作用靶点为组蛋白 H3 赖氨酸 27。研究报道 EZH2 参与了包括卵巢癌在内的多种肿瘤的发生发展。p16 是一种著名的细胞周期调节因子，已被证明在多种恶性细胞中是一种肿瘤抑制基因。然而，EZH2 与 p16 在卵巢癌中的调控关联仍有待充分阐明。本研究旨在确定 EZH2 是否通过调节 p16 的表达参与卵巢癌的发生发展。构建了 EZH2 短发夹 RNA（shRNA）慢病毒载体，并用于转导 A2780 和 SKOV3 卵巢癌细胞系。分别采用逆转录 - 定量聚合酶链反应和蛋白质印迹分析检测卵巢癌细胞中 EZH2 和 p16 的表达水平。使用 CCK - 8 检测法和 Transwell 检测法确定抑制 EZH2 对细胞增殖和迁移的作用。此外，利用裸鼠异种移植模型确定 EZH2 和 p16 在卵巢癌形成中的作用。结果显示，抑制 EZH2 可增加 p16 的表达，并抑制卵巢癌细胞的增殖和迁移能力。EZH2 表达下调可抑制卵巢肿瘤形成。研究结果表明，在卵巢癌中 p16 受 EZH2 负调控，且 p16 和 EZH2 在卵巢癌的肿瘤发生过程中起重要作用。EZH2 和 p16 代表了卵巢癌诊断的潜在生物标志物以及卵巢癌基因治疗的靶点。
