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Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma

雌激素通过PI3K-AKT通路上调子宫内膜癌中DNA2的表达

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概要

子宫内膜癌是最常见的子宫癌类型,占子宫癌病例的90%。本文通过临床研究,检测子宫内膜癌患者标本中雌激素受体(ER)和DNA复制ATP依赖性解旋酶/核酸酶(DNA2)的表达,并分析两者之间的关系。通过细胞培养实验研究ER调控DNA2表达的机制,证实其与PI3K-AKT通路有关。研究还发现,使用短发夹RNA(shRNA)特异性靶向降低Ishikawa中DNA2的表达,会导致细胞增殖和克隆形成能力降低。总的来说,本研究证实了DNA2作为治疗靶点的可行性,并证明抑制DNA2可使Ishikawa对喜树碱(CPT)化疗增敏。我们的发现为DNA2的潜在机制提供了新的见解,这将有助于开发与子宫内膜癌诊断和治疗相关的新方法。

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Acknowledgments

This work was supported by the General Projects of Medical and Health Science and Technology Plan in Zhejiang Province (No. 2020KY433), China.

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Correspondence to Ruolang Pan  (潘若浪) or Yan Yu  (余艳).

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Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Author contributions

All authors contributed to the study conception and design. Xinyan WANG and Xiuling XU designed the experiment. Ting ZHANG and Yang JIN performed the study. Sheng XU and Lifeng CHEN drafted the manuscript. Yucheng LAI and Ling ZHANG analyzed data. Ruolang PAN and Yan YU designed the experiment, revised the manuscript, and monitored the project progression. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

Compliance with ethics guidelines

Xinyan WANG, Xiuling XU, Ting ZHANG, Yang JIN, Sheng XU, Lifeng CHEN, Yucheng LAI, Ling ZHANG, Ruolang PAN, and Yan YU declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article. This study was granted by the Ethics Committee of Zhejiang Provincial People’s Hospital (November 9, 2019; No. 2019KY204).

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Wang, X., Xu, X., Zhang, T. et al. Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma. J. Zhejiang Univ. Sci. B 24, 262–268 (2023). https://doi.org/10.1631/jzus.B2200436

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  • DOI: https://doi.org/10.1631/jzus.B2200436

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