• 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

PLAA 通过 METTL3 介导的 TRPC3 mRNA 的 mA 修饰抑制卵巢癌细胞转移。

PLAA suppresses ovarian cancer metastasis via METTL3-mediated mA modification of TRPC3 mRNA.

机构信息

Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.

出版信息

Oncogene. 2022 Aug;41(35):4145-4158. doi: 10.1038/s41388-022-02411-w. Epub 2022 Jul 22.

DOI:10.1038/s41388-022-02411-w
PMID:35869392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9418004/
Abstract

Wide metastasis contributes to a high death rate in ovarian cancer, and understanding of the molecular mechanism helps to find effective targets for metastatic ovarian cancer therapy. It has been found that phospholipase A2-activating protein (PLAA) is inactivated in some cancers, but its role in cancer metastasis remains unknown. Here, we found that PLAA was significantly downregulated in ovarian cancer highly metastatic cell lines and patients, and the low expression of PLAA was associated with poorer prognosis and high-risk clinicopathological features of patients. PLAA inhibited the migration and invasion of ovarian cancer cells and metastasis of transplanted tumor in the orthotopic xenograft mouse model. Meanwhile, PLAA inhibited metastasis of ovarian cancer by inhibiting transient receptor potential channel canonical 3 (TRPC3)-mediated the intracellular Ca level. Mechanistically, PLAA inhibited methyltransferase-like 3 (METTL3) expression through the ubiquitin-mediated degradation, and METTL3 stabilized TRPC3 mRNA expression via N6-methyladenosine (mA) modification. Our study verified the function and mechanism of the PLAA-METTL3-TRPC3 axis involved in ovarian cancer metastasis, with a view to providing a potential therapeutic approach for ovarian cancer.

摘要

广泛转移导致卵巢癌死亡率高，了解其分子机制有助于找到转移性卵巢癌治疗的有效靶点。已经发现，磷脂酶 A2 激活蛋白 (PLAA) 在一些癌症中失活，但它在癌症转移中的作用尚不清楚。在这里，我们发现 PLAA 在卵巢癌高转移细胞系和患者中显著下调，PLAA 的低表达与患者预后不良和高风险临床病理特征相关。PLAA 抑制了卵巢癌细胞的迁移和侵袭以及原位异种移植小鼠模型中转移瘤的转移。同时，PLAA 通过抑制瞬时受体电位通道经典型 3 (TRPC3) 介导的细胞内 Ca 水平来抑制卵巢癌的转移。在机制上，PLAA 通过泛素介导的降解抑制甲基转移酶样 3 (METTL3) 的表达，METTL3 通过 N6-甲基腺苷 (mA) 修饰稳定 TRPC3 mRNA 的表达。本研究验证了 PLAA-METTL3-TRPC3 轴在卵巢癌转移中的功能和机制，以期为卵巢癌提供一种潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/af207cef467e/41388_2022_2411_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/06c75aa36f10/41388_2022_2411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/fbeb24e6bd1e/41388_2022_2411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/d9f66f8be1d6/41388_2022_2411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/189cfe5c3708/41388_2022_2411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/132d2efd62dd/41388_2022_2411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/65b0c0e60218/41388_2022_2411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/28306e206a40/41388_2022_2411_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/af207cef467e/41388_2022_2411_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/06c75aa36f10/41388_2022_2411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/fbeb24e6bd1e/41388_2022_2411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/d9f66f8be1d6/41388_2022_2411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/189cfe5c3708/41388_2022_2411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/132d2efd62dd/41388_2022_2411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/65b0c0e60218/41388_2022_2411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/28306e206a40/41388_2022_2411_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/905d/9418004/af207cef467e/41388_2022_2411_Fig8_HTML.jpg

相似文献

1
PLAA suppresses ovarian cancer metastasis via METTL3-mediated mA modification of TRPC3 mRNA.PLAA 通过 METTL3 介导的 TRPC3 mRNA 的 mA 修饰抑制卵巢癌细胞转移。
Oncogene. 2022 Aug;41(35):4145-4158. doi: 10.1038/s41388-022-02411-w. Epub 2022 Jul 22.
2
The m6A Methyltransferase METTL3-Mediated N6-Methyladenosine Modification of DEK mRNA to Promote Gastric Cancer Cell Growth and Metastasis.m6A 甲基转移酶 METTL3 介导的 DEK mRNA 的 N6-甲基腺苷化修饰促进胃癌细胞生长和转移。
Int J Mol Sci. 2022 Jun 9;23(12):6451. doi: 10.3390/ijms23126451.
3
FSH enhances the proliferation of ovarian cancer cells by activating transient receptor potential channel C3.FSH 通过激活瞬时受体电位通道 C3 促进卵巢癌细胞的增殖。
Endocr Relat Cancer. 2013 May 30;20(3):415-29. doi: 10.1530/ERC-12-0005. Print 2013 Jun.
4
METTL3/YTHDF1 mA axis promotes tumorigenesis by enhancing DDR2 expression in ovarian cancer.METTL3/YTHDF1 mA 轴通过增强 DDR2 表达促进卵巢癌发生。
Pathol Res Pract. 2024 Jan;253:155047. doi: 10.1016/j.prp.2023.155047. Epub 2023 Dec 21.
5
YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer.YTHDF2 通过 N6-甲基腺苷依赖性方式介导肿瘤抑制因子的 mRNA 降解，从而诱导前列腺癌中 AKT 的磷酸化。
Mol Cancer. 2020 Oct 29;19(1):152. doi: 10.1186/s12943-020-01267-6.
6
METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP.METTL3在子宫内膜样上皮性卵巢癌中独立于METTl14和WTAP调节m6A。
Cell Biol Int. 2020 Dec;44(12):2524-2531. doi: 10.1002/cbin.11459. Epub 2020 Sep 11.
7
METTL3 facilitates tumor progression via an mA-IGF2BP2-dependent mechanism in colorectal carcinoma.METTL3 通过 mA-IGF2BP2 依赖的机制促进结直肠癌的肿瘤进展。
Mol Cancer. 2019 Jun 24;18(1):112. doi: 10.1186/s12943-019-1038-7.
8
Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells.沉默 METTL3 可有效抑制前列腺癌细胞的侵袭和转移。
Theranostics. 2021 Jun 11;11(16):7640-7657. doi: 10.7150/thno.61178. eCollection 2021.
9
SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma.SUMO1 修饰的甲基转移酶样蛋白 3 通过调节肝细胞癌中 Snail mRNA 的动态平衡促进肿瘤进展。
Theranostics. 2020 Apr 27;10(13):5671-5686. doi: 10.7150/thno.42539. eCollection 2020.
10
N6-methyladenosine Methyltransferase METTL3 Enhances PTGER2 Expression to Increase Ovarian Cancer Stemness and Chemoresistance.N6-甲基腺苷甲基转移酶 METTL3 通过增强 PTGER2 的表达来增加卵巢癌细胞干性和化疗耐药性。
Front Biosci (Landmark Ed). 2023 Sep 14;28(9):199. doi: 10.31083/j.fbl2809199.

引用本文的文献

1
RNA Modifications in Health and Disease.健康与疾病中的RNA修饰
MedComm (2020). 2025 Sep 3;6(9):e70341. doi: 10.1002/mco2.70341. eCollection 2025 Sep.
2
IGF2BP2 binding to CPSF6 facilitates m6A-mediated alternative polyadenylation of PUM2 and promotes malignant progression in ovarian cancer.IGF2BP2与CPSF6结合促进PUM2的m6A介导的可变多聚腺苷酸化，并促进卵巢癌的恶性进展。
Clin Transl Med. 2025 Jul;15(7):e70388. doi: 10.1002/ctm2.70388.
3
PLAA/UFD-3 regulates P-bodies through its intrinsic disordered domain.PLAA/UFD-3通过其内在无序结构域调节P小体。

本文引用的文献

1
Primary and metastatic peritoneal surface malignancies.原发性和转移性腹膜表面恶性肿瘤。
Nat Rev Dis Primers. 2021 Dec 16;7(1):91. doi: 10.1038/s41572-021-00326-6.
2
The role of Ubiquitination in Apoptosis and Necroptosis.泛素化在细胞凋亡和坏死中的作用。
Cell Death Differ. 2022 Feb;29(2):272-284. doi: 10.1038/s41418-021-00922-9. Epub 2021 Dec 15.
3
The multicellular signalling network of ovarian cancer metastases.卵巢癌转移的细胞间信号网络。
Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2427250122. doi: 10.1073/pnas.2427250122. Epub 2025 Jun 25.
4
Integration of Bulk and Single-Cell RNA Sequencing to Identify RNA Modifications-Related Prognostic Signature in Ovarian Cancer.整合批量和单细胞RNA测序以鉴定卵巢癌中与RNA修饰相关的预后特征
Int J Gen Med. 2025 May 20;18:2629-2647. doi: 10.2147/IJGM.S523878. eCollection 2025.
5
KDM1A-mediated ZFP64 demethylation activates CENPL to promote epithelial ovarian cancer progression.KDM1A介导的ZFP64去甲基化激活CENPL以促进上皮性卵巢癌进展。
Cytotechnology. 2025 Feb;77(1):10. doi: 10.1007/s10616-024-00671-w. Epub 2024 Dec 1.
6
Stabilization of SQLE mRNA by WTAP/FTO/IGF2BP3-dependent manner in HGSOC: implications for metabolism, stemness, and progression.WTAP/FTO/IGF2BP3依赖性方式在高级别浆液性卵巢癌中对SQLE mRNA的稳定作用：对代谢、干性和进展的影响
Cell Death Dis. 2024 Dec 1;15(12):872. doi: 10.1038/s41419-024-07257-6.
7
Discovery of a potent and selective TRPC3 antagonist with neuroprotective effects.发现一种具有神经保护作用的强效且选择性的瞬时受体电位阳离子通道亚家族3（TRPC3）拮抗剂。
Bioorg Med Chem. 2025 Jan 1;117:118021. doi: 10.1016/j.bmc.2024.118021. Epub 2024 Nov 26.
8
Post-Translational Modifications of RNA-Modifying Proteins in Cellular Dynamics and Disease Progression.RNA 修饰蛋白的翻译后修饰在细胞动态和疾病进展中的作用。
Adv Sci (Weinh). 2024 Nov;11(44):e2406318. doi: 10.1002/advs.202406318. Epub 2024 Oct 8.
9
RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B.RAD51B-AS1 通过上调 RAD51B 促进卵巢癌的恶性生物学行为。
J Zhejiang Univ Sci B. 2024 Jul 15;25(7):581-593. doi: 10.1631/jzus.B2300154.
10
Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers.小细胞肺癌患者血液转录组谱的综合分析，以鉴定新的化疗耐药相关生物标志物。
Front Immunol. 2024 Jun 18;15:1338162. doi: 10.3389/fimmu.2024.1338162. eCollection 2024.
Clin Transl Med. 2021 Nov;11(11):e633. doi: 10.1002/ctm2.633.
4
Advances in TRP channel drug discovery: from target validation to clinical studies.TRP 通道药物发现的进展：从靶点确证到临床研究。
Nat Rev Drug Discov. 2022 Jan;21(1):41-59. doi: 10.1038/s41573-021-00268-4. Epub 2021 Sep 15.
5
METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246.METTL3通过促进初级微小RNA-1246的成熟来抑制CCNG2的表达，从而促进卵巢癌的发生和转移。
Cell Death Discov. 2021 Sep 8;7(1):237. doi: 10.1038/s41420-021-00600-2.
6
TRPC3 promotes tumorigenesis of gastric cancer via the CNB2/GSK3β/NFATc2 signaling pathway.瞬时受体电位通道蛋白3（TRPC3）通过钙调神经磷酸酶2（CNB2）/糖原合成酶激酶3β（GSK3β）/活化T细胞核因子c2（NFATc2）信号通路促进胃癌的肿瘤发生。
Cancer Lett. 2021 Oct 28;519:211-225. doi: 10.1016/j.canlet.2021.07.038. Epub 2021 Jul 24.
7
Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells.外泌体介导的高转移卵巢癌细胞 CD44 的转移促进低转移卵巢癌细胞的迁移和侵袭。
J Ovarian Res. 2021 Feb 24;14(1):38. doi: 10.1186/s13048-021-00776-2.
8
mA mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis.由METTL3启动的mA mRNA甲基化直接促进YAP翻译，并通过调节MALAT1-miR-1914-3p-YAP轴增加YAP活性，从而诱导非小细胞肺癌的耐药性和转移。
J Hematol Oncol. 2021 Feb 23;14(1):32. doi: 10.1186/s13045-021-01048-8.
9
The role of m6A modification in the biological functions and diseases.m6A 修饰在生物学功能和疾病中的作用。
Signal Transduct Target Ther. 2021 Feb 21;6(1):74. doi: 10.1038/s41392-020-00450-x.
10
Cancer Statistics, 2021.癌症统计数据，2021.
CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12.