• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

PADI2的下调通过在体外和体内单独或与奥拉帕尼联合抑制JAK2/STAT3信号通路来阻止卵巢癌的增殖和上皮-间质转化。

Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib.

作者信息

Liu Lidong, Zhang Zhiwei, Zhang Guoxiang, Wang Ting, Ma Yingchun, Guo Wei

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, People's Republic of China.

Medical Research Center, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, People's Republic of China.

出版信息

J Transl Med. 2020 Sep 20;18(1):357. doi: 10.1186/s12967-020-02528-0.

DOI:10.1186/s12967-020-02528-0
PMID:32951601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7504643/
Abstract

BACKGROUND

Epithelial ovarian cancer (EOC) is the most lethal disease among female genital malignant tumors. Peptidylarginine deiminase type II(PADI II) has been shown to enhance a variety of cancers carcinogenesis, including ovarian cancer. The purpose of this study was to investigate the biological role of PADI2 in ovarian cancer (OC) and the relative mechanism.

METHODS

Gene Expression Profiling Interactive Analysis (GEPIA) ( https://gepia.pku.cn/ ) and ONCOMINE ( https://www.oncomine.org/ ) were used to analyze PADI2 Gene Expression data. The survival curve for the PADI2 gene was generated by using the online Kaplan-Meier mapping site ( https://www.kmplot.com/ ). We conducted MTT assay, cloning formation assay and EdU cell proliferation assay to detect the cell activity of PADI2 knockdown A2780 and SKOV3 ovarian cancer cells treated with Olaparib. Cell migration and invasion were observed by would healing and transwell assay. The pathway changes after the treatment of PADI2 were detected by transcriptome sequencing and western blot. The role of PADI2 combined with Olaparib treatment in vivo was studied in nude mouse model bearing ovarian cancer tumor.

RESULTS

We investigated the role of PADI2 on EOC in vitro and in vivo. PADI2 was upregulated in ovarian cancer samples and high PADI2 expression was correlated with poor outcome. Downregulating PADI2 suppressed colony formation, proliferation, migration and invasion of A2780 and SKOV3 cells. Furthermore, downregulating PADI2 and Olaparib combination treatment attenuated the viability, migration and invasion of A2780 and SKOV3 cells. We identified differentially expressed genes in A2780-shPADI2 and SKOV3-shPADI2 cell by transcriptome sequencing analysis and verified that downregulating PADI2 and Olaparib combination treatment suppresses EMT and JAK2/STAT3 signaling pathway in A2780 and SKOV3 cells in vitro and in vivo.

CONCLUSIONS

Downregulation of PADI2 and Olaparib combination treatment attenuated the proliferation, migration and invasion of A2780 and SKOV3 cells by inhibiting the EMT through JAK2/STAT3 signaling pathway.

摘要

背景

上皮性卵巢癌（EOC）是女性生殖系统恶性肿瘤中致死率最高的疾病。II型肽基精氨酸脱亚氨酶（PADI II）已被证明可促进多种癌症的发生发展，包括卵巢癌。本研究旨在探讨PADI2在卵巢癌（OC）中的生物学作用及其相关机制。

方法

利用基因表达谱交互分析（GEPIA）（https://gepia.pku.cn/）和ONCOMINE（https://www.oncomine.org/）分析PADI2基因表达数据。通过在线Kaplan-Meier映射网站（https://www.kmplot.com/）生成PADI2基因的生存曲线。我们进行了MTT试验、克隆形成试验和EdU细胞增殖试验，以检测用奥拉帕尼处理的PADI2敲低的A2780和SKOV3卵巢癌细胞的细胞活性。通过伤口愈合试验和Transwell试验观察细胞迁移和侵袭情况。通过转录组测序和蛋白质免疫印迹检测PADI2处理后的信号通路变化。在荷卵巢癌肿瘤的裸鼠模型中研究PADI2联合奥拉帕尼治疗在体内的作用。

结果

我们在体外和体内研究了PADI2对EOC的作用。PADI2在卵巢癌样本中上调，高PADI2表达与不良预后相关。下调PADI2可抑制A2780和SKOV3细胞的集落形成、增殖、迁移和侵袭。此外，下调PADI2与奥拉帕尼联合治疗可减弱A2780和SKOV3细胞的活力、迁移和侵袭能力。通过转录组测序分析，我们在A2780-shPADI2和SKOV3-shPADI2细胞中鉴定出差异表达基因，并证实下调PADI2与奥拉帕尼联合治疗在体外和体内均可抑制A2780和SKOV3细胞中的上皮-间质转化（EMT）和JAK2/STAT3信号通路。

结论

下调PADI2与奥拉帕尼联合治疗通过JAK2/STAT3信号通路抑制EMT，从而减弱A2780和SKOV3细胞的增殖、迁移和侵袭能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/54eb9b68dd14/12967_2020_2528_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/999f42b01068/12967_2020_2528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/495ee3f11d8a/12967_2020_2528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/69082d666b63/12967_2020_2528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/2271d0a9e6ee/12967_2020_2528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/0c8f9cb1e1b2/12967_2020_2528_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/a96a024aa348/12967_2020_2528_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/0670a85ae977/12967_2020_2528_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/922db0ac7846/12967_2020_2528_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/d67be9054546/12967_2020_2528_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/54eb9b68dd14/12967_2020_2528_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/999f42b01068/12967_2020_2528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/495ee3f11d8a/12967_2020_2528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/69082d666b63/12967_2020_2528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/2271d0a9e6ee/12967_2020_2528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/0c8f9cb1e1b2/12967_2020_2528_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/a96a024aa348/12967_2020_2528_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/0670a85ae977/12967_2020_2528_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/922db0ac7846/12967_2020_2528_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/d67be9054546/12967_2020_2528_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d54a/7504643/54eb9b68dd14/12967_2020_2528_Fig10_HTML.jpg

相似文献

1
Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib.PADI2的下调通过在体外和体内单独或与奥拉帕尼联合抑制JAK2/STAT3信号通路来阻止卵巢癌的增殖和上皮-间质转化。
J Transl Med. 2020 Sep 20;18(1):357. doi: 10.1186/s12967-020-02528-0.
2
Preclinical evaluation of olaparib and metformin combination in BRCA1 wildtype ovarian cancer.奥拉帕利与二甲双胍联合用于BRCA1野生型卵巢癌的临床前评估。
Gynecol Oncol. 2016 Aug;142(2):323-31. doi: 10.1016/j.ygyno.2016.06.005. Epub 2016 Jun 16.
3
CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway.CNOT7 通过 AKT 信号通路调节卵巢癌细胞的生物学功能。
Life Sci. 2021 Mar 1;268:118996. doi: 10.1016/j.lfs.2020.118996. Epub 2021 Jan 4.
4
SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway.SPTBN1 通过 SOCS3 介导的阻断 JAK/STAT3 信号通路抑制上皮性卵巢癌的进展。
Aging (Albany NY). 2020 Jun 8;12(11):10896-10911. doi: 10.18632/aging.103303.
5
The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell.SB202190与SP600125的药物组合显著抑制奥拉帕尼耐药卵巢癌细胞的生长和转移。
Curr Pharm Biotechnol. 2018;19(6):506-513. doi: 10.2174/1389201019666180713102656.
6
Lysine demethylase 2A promotes the progression of ovarian cancer by regulating the PI3K pathway and reversing epithelial‑mesenchymal transition.赖氨酸去甲基化酶 2A 通过调节 PI3K 通路和逆转上皮-间充质转化促进卵巢癌的进展。
Oncol Rep. 2019 Feb;41(2):917-927. doi: 10.3892/or.2018.6888. Epub 2018 Nov 27.
7
Overexpression of long noncoding RNA HOXB-AS3 indicates an unfavorable prognosis and promotes tumorigenesis in epithelial ovarian cancer via Wnt/β-catenin signaling pathway.长链非编码RNA HOXB-AS3的过表达提示上皮性卵巢癌预后不良，并通过Wnt/β-连环蛋白信号通路促进肿瘤发生。
Biosci Rep. 2019 Aug 2;39(8). doi: 10.1042/BSR20190906. Print 2019 Aug 30.
8
LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells.LDH-A 抑制剂作为增敏剂增强 PARP 抑制剂在卵巢癌细胞中的抗癌作用。
Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780.
9
The anti-tumor effect of OP-B on ovarian cancer in vitro and in vivo, and its mechanism: An investigation using network pharmacology-based analysis.基于网络药理学分析的 OP-B 对卵巢癌的体内外抗肿瘤作用及其机制研究。
J Ethnopharmacol. 2022 Jan 30;283:114706. doi: 10.1016/j.jep.2021.114706. Epub 2021 Oct 3.
10
MicroRNA‑195 suppresses cell proliferation, migration and invasion in epithelial ovarian carcinoma via inhibition of the CDC42/CCND1 pathway.MicroRNA-195 通过抑制 CDC42/CCND1 通路抑制上皮性卵巢癌中的细胞增殖、迁移和侵袭。
Int J Mol Med. 2020 Nov;46(5):1862-1872. doi: 10.3892/ijmm.2020.4716. Epub 2020 Aug 31.

引用本文的文献

1
Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.靶向 PADI2 抑制 EMT 介导的迁移和侵袭以及 CCL3/5 诱导的血管生成，作为口腔癌转移的潜在治疗策略。
Clin Exp Metastasis. 2024 Dec;41(6):925-935. doi: 10.1007/s10585-024-10310-5. Epub 2024 Aug 31.
2
Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations.转录组和蛋白质组中骨髓间充质祖细胞群体对衰老的差异反应。
J Gerontol A Biol Sci Med Sci. 2024 Sep 1;79(9). doi: 10.1093/gerona/glae147.
3
Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

本文引用的文献

1
TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1.TGF-β 通过 RAS 效应因子 RREB1 来协调纤维化和发育性 EMT。
Nature. 2020 Jan;577(7791):566-571. doi: 10.1038/s41586-019-1897-5. Epub 2020 Jan 8.
2
Gamma ray-induced in vitro cell migration via EGFR/ERK/Akt/p38 activation is prevented by olaparib pretreatment.奥拉帕尼预处理可阻止伽马射线诱导的 EGFR/ERK/Akt/p38 激活的细胞迁移。
Int J Radiat Biol. 2020 May;96(5):651-660. doi: 10.1080/09553002.2020.1711461. Epub 2020 Feb 6.
3
Cancer statistics, 2020.
间充质祖细胞群体转录组和蛋白质组对衰老的不同反应。
Res Sq. 2023 Dec 15:rs.3.rs-3755129. doi: 10.21203/rs.3.rs-3755129/v1.
4
Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management.细胞膜唾液酸组：唾液酸作为人类癌症治疗中的治疗靶点和耐药性调节剂
Cancers (Basel). 2023 Oct 22;15(20):5103. doi: 10.3390/cancers15205103.
5
Peptidylarginine Deiminase Type 2 Predicts Tumor Progression and Poor Prognosis in Patients with Curatively Resected Biliary Tract Cancer.2型肽基精氨酸脱亚氨酶预测根治性切除胆管癌患者的肿瘤进展和不良预后
Cancers (Basel). 2023 Aug 16;15(16):4131. doi: 10.3390/cancers15164131.
6
Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice.蛋白精氨酸脱亚氨酶 II 的抑制作用可抑制小鼠原位移植中的视网膜母细胞瘤。
Oncol Rep. 2023 Jul;50(1). doi: 10.3892/or.2023.8583. Epub 2023 Jun 16.
7
Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.PADI 家族在炎症性自身免疫性疾病和癌症中的作用：系统评价。
Front Immunol. 2023 Mar 20;14:1115794. doi: 10.3389/fimmu.2023.1115794. eCollection 2023.
8
Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases†.精氨酸脱亚氨酶酶和瓜氨酸化蛋白在女性生殖生理学及相关疾病中的作用。
Biol Reprod. 2022 Dec 10;107(6):1395-1410. doi: 10.1093/biolre/ioac173.
9
ROS-induced PADI2 downregulation accelerates cellular senescence via the stimulation of SASP production and NFκB activation.ROS 诱导的 PADI2 下调通过刺激 SASP 产生和 NFκB 激活加速细胞衰老。
Cell Mol Life Sci. 2022 Feb 26;79(3):155. doi: 10.1007/s00018-022-04186-5.
10
Ribonucleotide reductase subunit M2 promotes proliferation and epithelial-mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma.核糖核苷酸还原酶亚基 M2 通过 JAK2/STAT3 信号通路促进视网膜母细胞瘤的增殖和上皮-间充质转化。
Bioengineered. 2021 Dec;12(2):12800-12811. doi: 10.1080/21655979.2021.2001241.
癌症统计数据，2020 年。
CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
4
Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6.长非编码 RNA RP11-468E2.5 通过靶向 STAT5 和 STAT6 抑制 JAK/STAT 信号通路从而抑制结直肠癌细胞增殖并促进其凋亡。
J Exp Clin Cancer Res. 2019 Nov 12;38(1):465. doi: 10.1186/s13046-019-1428-0.
5
Differential Expression of TOM34, AL1A1, PADI2 and KLRBA in NNK Induced Lung Cancer in Wistar Rats and their Implications.TOM34、AL1A1、PADI2 和 KLRBA 在 NNK 诱导的 Wistar 大鼠肺癌中的差异表达及其意义。
Curr Cancer Drug Targets. 2019;19(11):919-929. doi: 10.2174/1871525717666190717162646.
6
Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer.抑制非小细胞肺癌中 PARP-1 可增强碳离子照射后通过抑制 EGFR/Akt/p38/ERK 信号通路和上皮-间充质转化降低转移潜能。
BMC Cancer. 2019 Aug 22;19(1):829. doi: 10.1186/s12885-019-6015-4.
7
Synthetic lethality between BRCA1 deficiency and poly(ADP-ribose) polymerase inhibition is modulated by processing of endogenous oxidative DNA damage.BRCA1 缺陷与聚（ADP-核糖）聚合酶抑制之间的合成致死性受内源性氧化 DNA 损伤的处理调节。
Nucleic Acids Res. 2019 Sep 26;47(17):9132-9143. doi: 10.1093/nar/gkz624.
8
Chlorambucil targets BRCA1/2-deficient tumours and counteracts PARP inhibitor resistance.苯丁酸氮芥靶向 BRCA1/2 缺陷型肿瘤并克服 PARP 抑制剂耐药性。
EMBO Mol Med. 2019 Jul;11(7):e9982. doi: 10.15252/emmm.201809982. Epub 2019 May 24.
9
Peptidyl Arginine Deiminase, Type II (PADI2) Is Involved in Urothelial Bladder Cancer.Ⅱ型肽基精氨酸脱亚氨酶（PADI2）参与膀胱癌的发生。
Pathol Oncol Res. 2020 Apr;26(2):1279-1285. doi: 10.1007/s12253-019-00687-0. Epub 2019 Jul 2.
10
Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells.姜黄素通过抑制 AKT/mTOR/p70S6K 通路诱导人卵巢癌细胞凋亡和自噬。
Arch Gynecol Obstet. 2019 Jun;299(6):1627-1639. doi: 10.1007/s00404-019-05058-3. Epub 2019 Apr 21.