文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

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。

Lysine demethylase 2A promotes the progression of ovarian cancer by regulating the PI3K pathway and reversing epithelial‑mesenchymal transition.

机构信息

Department of Gynaecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of Pathology, Molecular Diagnostics Laboratory, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Oncol Rep. 2019 Feb;41(2):917-927. doi: 10.3892/or.2018.6888. Epub 2018 Nov 27.

DOI:10.3892/or.2018.6888
PMID:30483796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6313075/
Abstract

Metastasis is the most common cause of death in ovarian cancer patients but remains largely untreated. Epithelial‑mesenchymal transition (EMT) is critical for the conversion of early‑stage ovarian tumors into metastatic malignancies. Thus, investigating the signaling pathways promoting EMT may identify potential targets for the treatment of metastatic ovarian cancer. Lysine demethylase 2A (KDM2A), also known as FBXL11 and JHDM1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates EMT and the metastasis of ovarian cancer. However, the function and underlying mechanisms of EMT suppression in ovarian cancer have not been thoroughly elucidated to date. In the present study, we used Gene Expression Omnibus (GEO) databases to determine that KDM2A is significantly upregulated in human ovarian cancers. KDM2A expression was assessed by immunohistochemistry of epithelial ovarian cancer (EOC) borderline ovarian tumors and normal ovary tissues. Seven fresh EOC tissues and 3 fresh normal ovary tissues were collected for western blot analysis. Kaplan‑Meier survival curves were constructed to identify genes related to EOC prognosis from the TCGA data portal. Stable KDM2A‑knockdown cell lines were established to study the biological functions and underlying mechanisms of KDM2A in EMT in vitro. GEO database analysis revealed that KDM2A was highly upregulated in EOC tissues; this analysis was accompanied by immunochemistry and western blot analysis using samples of human tissues. High expression of KDM2A was associated with poor survival in EOC patients. KDM2A knockdown promoted apoptosis and suppressed the proliferation, migration and invasion of tumor cells in vitro. EMT and the PI3K/AKT/mTOR signaling pathway were suppressed in KDM2A‑silenced cells. Inactivation of the PI3K/AKT/mTOR signaling pathway in A2780 cells induced EMT inhibition. Our data revealed that KDM2A functions as a tumor oncogene, and the downregulation of KDM2A expression regulates EMT and EOC progression, providing a valuable prognostic marker and potential target for the treatment of EOC patients.

摘要

转移是卵巢癌患者死亡的最常见原因，但目前仍缺乏有效的治疗方法。上皮-间充质转化（EMT）对于将早期卵巢肿瘤转化为转移性恶性肿瘤至关重要。因此，研究促进 EMT 的信号通路可能为治疗转移性卵巢癌找到潜在的靶点。赖氨酸去甲基酶 2A（KDM2A），也称为 FBXL11 和 JHDM1A，是一种组蛋白 H3 赖氨酸 36（H3K36）去甲基酶，可调节 EMT 和卵巢癌的转移。然而，迄今为止，EMT 抑制在卵巢癌中的作用及其潜在机制尚未得到充分阐明。在本研究中，我们使用基因表达综合数据库（GEO）确定 KDM2A 在人类卵巢癌中显著上调。通过免疫组化分析上皮性卵巢癌（EOC）交界性卵巢肿瘤和正常卵巢组织评估 KDM2A 的表达。收集了 7 例新鲜的 EOC 组织和 3 例新鲜的正常卵巢组织进行 Western blot 分析。通过 TCGA 数据门户构建 Kaplan-Meier 生存曲线，确定与 EOC 预后相关的基因。建立稳定的 KDM2A 敲低细胞系，以研究 KDM2A 在 EMT 中的生物学功能和潜在机制。GEO 数据库分析显示，KDM2A 在 EOC 组织中高度上调；该分析伴随免疫组化和 Western blot 分析，使用了人类组织样本。KDM2A 高表达与 EOC 患者生存不良相关。KDM2A 敲低促进了细胞凋亡，并抑制了肿瘤细胞的增殖、迁移和侵袭。在沉默 KDM2A 的细胞中抑制了 EMT 和 PI3K/AKT/mTOR 信号通路。在 A2780 细胞中抑制 PI3K/AKT/mTOR 信号通路诱导 EMT 抑制。我们的数据表明，KDM2A 作为一种肿瘤癌基因发挥作用，下调 KDM2A 表达可调节 EMT 和 EOC 进展，为 EOC 患者提供了有价值的预后标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/9a76b979371e/OR-41-02-0917-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/7b12dff9f84e/OR-41-02-0917-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/2e340fea2fb9/OR-41-02-0917-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/f5a70e8989bc/OR-41-02-0917-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/08fe92cf3a12/OR-41-02-0917-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/9a76b979371e/OR-41-02-0917-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/7b12dff9f84e/OR-41-02-0917-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/2e340fea2fb9/OR-41-02-0917-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/f5a70e8989bc/OR-41-02-0917-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/08fe92cf3a12/OR-41-02-0917-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b1/6313075/9a76b979371e/OR-41-02-0917-g04.jpg

相似文献

[1]
Lysine demethylase 2A promotes the progression of ovarian cancer by regulating the PI3K pathway and reversing epithelial‑mesenchymal transition.

Oncol Rep. 2018-11-27

[2]
TRIP13-induced NUSAP1 upregulation promotes CcRCC progression through EMT and PI3K/AKT/mTOR pathway.

J Transl Med. 2025-8-11

[3]
IGF2BP1 promotes the progression of head and neck squamous cell carcinoma by activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition.

World J Surg Oncol. 2025-7-14

[4]
Upregulated SAE1 Drives Tumorigenesis and Is Associated with Poor Clinical Outcomes in Breast Cancer.

Breast J. 2024-6-30

[5]
PLAGL2 as a prognostic biomarker and an EMT-promoting factor in PDAC.

Sci Rep. 2025-7-14

[6]
Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer.

Cancer Med. 2024-9

[7]
Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway.

Sci China Life Sci. 2024-9

[8]
Zinc finger protein 695 facilitates the proliferation of colorectal cancer cells through activation of the NEK2 and PI3K/Akt/mTOR signaling pathways.

Oncol Rep. 2025-10

[9]
Impact of residual disease as a prognostic factor for survival in women with advanced epithelial ovarian cancer after primary surgery.

Cochrane Database Syst Rev. 2022-9-26

[10]
Caveolin-1 inhibits the proliferation and invasion of lung adenocarcinoma via EGFR degradation.

Sci Rep. 2025-7-1

引用本文的文献

[1]
In vivo CRISPR screening reveals epigenetic regulators of hepatobiliary plasticity.

Genes Dev. 2025-5-2

[2]
Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis.

Cell Oncol (Dordr). 2024-4

[3]
FZD1/KLF10-hsa-miR-4762-5p/miR-224-3p-circular RNAs axis as prognostic biomarkers and therapeutic targets for glioblastoma: a comprehensive report.

BMC Med Genomics. 2023-2-8

[4]
Autophagy in Cancer: A Metabolic Perspective.

Subcell Biochem. 2022

[5]
Recent Advances in the Aging Microenvironment of Breast Cancer.

Cancers (Basel). 2022-10-12

[6]
CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells.

Curr Issues Mol Biol. 2022-4-7

[7]
Histone H3K36me2 demethylase KDM2A promotes bladder cancer progression through epigenetically silencing RARRES3.

Cell Death Dis. 2022-6-13

[8]
CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma.

Aging (Albany NY). 2022-6-9

[9]
Epigenetic modification regulates tumor progression and metastasis through EMT (Review).

Int J Oncol. 2022-6

[10]
Cellular senescence, rejuvenation and potential immortality.

Proc Biol Sci. 2022-3-9

本文引用的文献

[1]
Magnolol Inhibits Human Glioblastoma Cell Migration by Regulating N-Cadherin.

J Neuropathol Exp Neurol. 2018-6-1

[2]
Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma.

Int J Biol Markers. 2018-4-1

[3]
γ-Glutamyl cyclotransferase contributes to tumor progression in high grade serous ovarian cancer by regulating epithelial-mesenchymal transition via activating PI3K/AKT/mTOR pathway.

Gynecol Oncol. 2018-2-9

[4]
Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders.

Am J Hum Genet. 2017-12-21

[5]
Tumorigenesis as a process of gradual loss of original cell identity and gain of properties of neural precursor/progenitor cells.

Cell Biosci. 2017-11-7

[6]
Lysine demethylase KDM2A inhibits TET2 to promote DNA methylation and silencing of tumor suppressor genes in breast cancer.

Oncogenesis. 2017-8-7

[7]
Human chorionic gonadotropin β regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer.

Oncol Rep. 2017-9

[8]
Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells.

J Biol Chem. 2017-8-4

[9]
Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition.

Br J Cancer. 2017-5-9

[10]
MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells.

Autophagy. 2017-2

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索