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ADAR1 具有致癌功能,可作为宫颈癌的预后因素。

ADAR1 has an oncogenic function and can be a prognostic factor in cervical cancer.

机构信息

Department 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.

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Kita-Ku, Okayama, 700-8558, Japan.

出版信息

Sci Rep. 2023 Mar 23;13(1):4720. doi: 10.1038/s41598-023-30452-y.

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.

摘要

RNA 结合蛋白 ADAR1 在人类癌症中发挥关键致癌作用

腺苷脱氨酶作用于 RNA 1(ADAR1)是一种最近描述的表观遗传修饰物,被认为在人类癌症中发挥关键致癌作用。然而,其在宫颈癌(CC)中的功能作用和临床意义尚不清楚。进行 ADAR1 敲低实验,以研究其在 SiHa(HPV16)、HeLa(HPV18)和 Yumoto(非 HPV)CC 细胞系中的致癌功能。检查细胞质和核 ADAR1 的表达,以阐明其与 CC 患者临床病理参数和预后的相关性。这导致 HPV16 型 SiHa、HPV18 型 HeLa 和非 HPV 型 Yumoto CC 细胞系中的细胞凋亡和坏死增加。细胞质和核 ADAR1 高表达的患者无进展生存期(PFS)较差(P=0.016)。多变量分析表明,细胞质和核 ADAR1 高表达的组合是 CC 患者预后的独立预测因素(P=0.017)。ADAR1 可能成为 HPV 阳性或 HPV 阴性 CC 的潜在治疗靶点。细胞质和核 ADAR1 的组合是 CC 更好的预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f7/10036526/ced10064fe4b/41598_2023_30452_Fig1_HTML.jpg

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