IMR Press / FBL / Volume 28 / Issue 9 / DOI: 10.31083/j.fbl2809199
Open Access Original Research
N6-methyladenosine Methyltransferase METTL3 Enhances PTGER2 Expression to Increase Ovarian Cancer Stemness and Chemoresistance
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1 Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 350014 Fuzhou, Fujian, China
2 Department of Radiation Oncology, Fujian Medical University Union Hospital, 350001 Fuzhou, Fujian, China
3 Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), 350001 Fuzhou, Fujian, China
4 Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), 350001 Fuzhou, Fujian, China
*Correspondence: (Yi-Bin Lin); (Ben-Hua Xu)
Front. Biosci. (Landmark Ed) 2023, 28(9), 199;
Revised: 7 April 2023 | Accepted: 9 May 2023 | Published: 14 September 2023
(This article belongs to the Special Issue Diagnostic, Prognostic, and Therapeutic Biomarkers for Ovarian Cancer)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

ovarian cancer
2021QH1141/Fujian Medical University
Fig. 1.
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