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ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer
Keiichiro Nakamura1, Kunitoshi Shigeyasu2, Kazuhiro Okamoto3
1Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan. k-nakamu@cc.okayama-u.ac.jp.
Abstract:
Adenosine deaminase acting on RNA 1 (ADAR1), a recently described epigenetic modifier, is believed to play a critical oncogenic role in human cancers. However, its functional role and clinical significance in cervical cancer (CC) remain unclear. ADAR1 knockdown was performed to investigate its oncogenic functions in SiHa (HPV16), HeLa (HPV18), and Yumoto (non-HPV) CC cell lines. Cytoplasmic and nuclear ADAR1 expression were examined to clarify their correlation with clinicopathological parameters and prognosis in patients with CC. This resulted in increased apoptosis and necroptosis in HPV16 -type SiHa, HPV18-type HeLa, and non-HPV-type Yumoto CC cell lines. Progression-free survival (PFS) rates of patients exhibiting high cytoplasmic and nuclear ADAR1 expression were poorer than those in the other groups (P = 0.016). Multivariate analysis indicated that the combination of higher cytoplasmic and nuclear ADAR1 expression was an independent predictor of prognosis in patients with CC (P = 0.017). ADAR1 could be a potential therapeutic target for HPV-positive or HPV-negative CC. The combination of cytoplasmic and nuclear ADAR1 comprises a better prognostic factor for CC.
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