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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Xinyan WANG, Xiuling XU, Ting ZHANG, Yang JIN, Sheng XU, Lifeng CHEN, Yucheng LAI, Ling ZHANG, Ruolang PAN, Yan YU. Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma[J]. Journal of Zhejiang University Science B, 2023, 24(6): 262-268.

@article{title="Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma",
author="Xinyan WANG, Xiuling XU, Ting ZHANG, Yang JIN, Sheng XU, Lifeng CHEN, Yucheng LAI, Ling ZHANG, Ruolang PAN, Yan YU",
journal="Journal of Zhejiang University Science B",
volume="24",
number="3",
pages="262-268",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200436"
}

%0 Journal Article
%T Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma
%A Xinyan WANG
%A Xiuling XU
%A Ting ZHANG
%A Yang JIN
%A Sheng XU
%A Lifeng CHEN
%A Yucheng LAI
%A Ling ZHANG
%A Ruolang PAN
%A Yan YU
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 3
%P 262-268
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer

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T1 - Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma
A1 - Xinyan WANG
A1 - Xiuling XU
A1 - Ting ZHANG
A1 - Yang JIN
A1 - Sheng XU
A1 - Lifeng CHEN
A1 - Yucheng LAI
A1 - Ling ZHANG
A1 - Ruolang PAN
A1 - Yan YU
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 3
SP - 262
EP - 268
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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Abstract
Chinese Summary
Academic Network
Reviewer Comment

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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Reference

[1]BeanJR, HosfordSR, SymondsLK, et al., 2015. The PI3K/mTOR dual inhibitor P7170 demonstrates potent activity against endocrine-sensitive and endocrine-resistant ER+ breast cancer. Breast Cancer Res Treat, 149(1):69-79.

[2]ConstantineGD, KesslerG, GrahamS, et al., 2019. Increased incidence of endometrial cancer following the women’s health initiative: an assessment of risk factors. J Womens Health (Larchmt), 28(2):237-243.

[3]DuanL, CalhounS, ShimD, et al., 2021. Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells. J Mol Cell Biol, 13(6):433-444.

[4]GaoCX, ShiJM, ZhangJX, et al., 2022. Chemerin promotes proliferation and migration of ovarian cancer cells by upregulating expression of PD-L1. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(2):164-170.

[5]HanYY, ZhangZY, WangZ, et al., 2021. Increased expression of DNA2 was linked to poor prognosis in breast cancer. Dis Markers, 2021:8860728.

[6]HassonSP, RubinekT, RyvoL, et al., 2013. Endocrine resist

[7]ance in breast cancer: focus on the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway. Breast Care (Basel), 8(4):248-255.

[8]JiaPP, JunaidM, MaYB, et al., 2017. Role of human DNA2 (hDNA2) as a potential target for cancer and other diseases: a systematic review. DNA Repair (Amst), 59:9-19.

[9]LiCH, WangCH, 2021. LG-ESSs and HG-ESSs: underlying molecular alterations and potential therapeutic strategies. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(8):‍633-646.

[10]LuoJ, SongZM, ZhangT, et al., 2022. Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(2):158-163.

[11]MoriceP, LearyA, CreutzbergC, et al., 2016. Endometrial cancer. Lancet, 387(10023):1094-1108.

[12]SetiawanVW, YangHP, PikeMC, et al., 2013. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol, 31(20):2607-2618.

[13]StraussC, KornowskiM, BenvenistyA, et al., 2014. The DNA2 nuclease/helicase is an estrogen-dependent gene mutated in breast and ovarian cancers. Oncotarget, 5(19):9396-9409.

[14]ThakarT, LeungW, NicolaeCM, et al., 2020. Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly. Nat Commun, 11:2147.

[15]UlrichLSG, 2011. Endometrial cancer, types, prognosis, female hormones and antihormones. Climacteric, 14(4):418-425.

[16]VassardD, SchmidtL, GlazerCH, et al., 2019. Assisted reproductive technology treatment and risk of ovarian cancer—a nationwide population-based cohort study. Hum Reprod, 34(11):2290-2296.

[17]ZhengL, ZhouM, GuoZG, et al., 2008. Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates. Mol Cell, 32(3):325-336.

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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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