Study on the effects and mechanism of RRM2 on three gynecological malignancies

Abstract

Cervical cancer, endometrial cancer, and ovarian cancer are the three most common gynecological malignancies. Their occurrence seriously affects women's health and life. Despite aggressive treatments, some patients still find it difficult to benefit from available therapies. Ribonucleic acid reductase subunit M2 (RRM2) is a limiting RNR enzyme involved in DNA synthesis and damage repair and plays a crucial role in many key cellular processes such as cell proliferation, migration, invasion, and senescence. Many studies have also shown that RRM2 also has a significant impact on tumor progression. However, the role of RRM2 in gynecological tumors has not been systematically studied. Our bioinformatics analysis of datasets related to cervical, endometrial, and ovarian cancers revealed that RRM2 is a significantly differentially expressed gene common to these cancers. We found that RRM2 was significantly overexpressed in cervical, endometrial, and ovarian cancer tissues and cells, exhibiting overall pro-oncogenic effects. RRM2 promoted cell proliferation, migration invasion, angiogenesis, and cell cycle in gynecological tumors while inhibiting apoptosis. The potential oncogenic effects of RRM2 in gynecologic tumor cell lines were further demonstrated using the RRM2 inhibitor Triapine (3-AP). These pro-tumorigenic effects may then be mediated through the involvement of RRM2 in the p53 and Akt/mTOR signaling pathways, altering the expression of p53 and Akt/mTOR. Thus, RRM2 is potentially a candidate gene for the unified diagnosis of cervical, endometrial, and ovarian cancers.