Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 350014 Fuzhou, Fujian, China.
Department of Radiation Oncology, Fujian Medical University Union Hospital, 350001 Fuzhou, Fujian, China.
Front Biosci (Landmark Ed). 2023 Sep 14;28(9):199. doi: 10.31083/j.fbl2809199.
Ovarian cancer is the second leading cause of gynecologic cancer-associated deaths. Cancer stemness and chemoresistance are responsible for ovarian cancer metastasis and the poor prognosis of patients. In this study, we determined the function of N6-methyladenine (m6A) RNA methylation and prostaglandin E receptor 2 (PTGER2) in ovarian cancer progression.
The m6A RNA methylation-associated PTGER2 in ovarian cancer was identified using bioinformatics analysis. The role of PTGER2 in ovarian cancer was elucidated in cell lines and clinical samples with cellular and molecular experiments.
In this investigation, bioinformatics analysis based on a public cancer database was used to elucidate the impact of m6A modification on the prognosis of patients with ovarian cancer. Moreover, PTGER2 was identified as a potential oncogene associated with the distant metastasis of ovarian cancer and poor patient prognosis. Interestingly, PTGER2 expression was experimentally shown to be enhanced by N6-adenosine-methyltransferase 70 kDa subunit (METTL3)-mediated m6A modification. In addition, PTGER2 enhanced cancer stem cell self-renewal properties, the epithelial-mesenchymal transition, and DNA damage repair, thus potentiating cell stemness, therapy resistance to carboplatin, proliferation, and metastasis of ovarian cancer. Importantly, PTGER2 expression in clinical samples was associated with distant metastasis, predicted poor patient prognosis, and independently served as a prognostic predictor in ovarian cancer.
Our work defines PTGER2 as an oncogene and reveals that PTGER2 is a prognostic predictor and novel therapeutic target for the management of ovarian cancer.
卵巢癌是妇科癌症相关死亡的第二大主要原因。癌症干性和化疗耐药性是导致卵巢癌转移和患者预后不良的原因。在本研究中，我们确定了 N6-甲基腺嘌呤（m6A）RNA 甲基化和前列腺素 E 受体 2（PTGER2）在卵巢癌进展中的作用。
使用生物信息学分析确定卵巢癌中与 m6A RNA 甲基化相关的 PTGER2。通过细胞和分子实验在细胞系和临床样本中阐明 PTGER2 在卵巢癌中的作用。
在这项研究中，使用公共癌症数据库进行的生物信息学分析阐明了 m6A 修饰对卵巢癌患者预后的影响。此外，PTGER2 被鉴定为与卵巢癌远处转移和患者预后不良相关的潜在癌基因。有趣的是，实验表明，N6-腺苷-甲基转移酶 70kDa 亚基（METTL3）介导的 m6A 修饰增强了 PTGER2 的表达。此外，PTGER2 增强了癌症干细胞自我更新特性、上皮-间充质转化和 DNA 损伤修复，从而增强了细胞干性、对卡铂的治疗耐药性、增殖和卵巢癌转移。重要的是，临床样本中 PTGER2 的表达与远处转移相关，预测患者预后不良，并可作为卵巢癌的独立预后预测因子。
我们的工作将 PTGER2 定义为一种癌基因，并揭示了 PTGER2 是卵巢癌管理的预后预测因子和新的治疗靶点。
