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 N-methyladenine (mA) RNA methylation and
prostaglandin E receptor 2 (PTGER2) in ovarian cancer progression.
Methods: The mA 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 mA 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
N-adenosine-methyltransferase 70 kDa subunit (METTL3)-mediated mA
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.