JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

Author(s): Xinyan WANG, Xiuling XU, Ting ZHANG, Yang JIN, Sheng XU, Lifeng CHEN, Yucheng LAI, Ling ZHANG, Ruolang PAN, Yan YU
Affiliation(s): Department of Gynecology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China; more
Corresponding email(s): panrl@zju.edu.cn, m05yuyan1@zju.edu.cn
Key Words: Endometrial cancer; Estrogen receptor; DNA2; PI3K-AKT

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Abstract: Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.

雌激素通过PI3K-AKT通路上调子宫内膜癌中DNA2的表达

王鑫炎¹，徐秀玲²，张婷¹，金央²，徐盛³，陈莉锋³，赖雨程³，张玲^4,5，潘若浪^4,5，余艳³
¹浙江省中医院，浙江中医药大学第一附属医院妇科，中国杭州市， 310006
²浙江中医药大学附属杭州市中医院，杭州市中医院妇产科，中国杭州市， 310005
³浙江省人民医院，杭州医学院附属人民医院妇科，中国杭州市， 310014
⁴浙江省细胞药物与应用技术研究重点实验室，中国杭州市， 311122
⁵浙江省易文赛细胞药物和制品研究院，中国杭州市， 311122
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。

关键词组：子宫内膜癌；雌激素受体；DNA2；PI3K-AKT通路

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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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