• 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

METTL3 通过 m6A 修饰介导的 NEK2 上调促进宫颈癌的进展。

METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2.

机构信息

Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou University, 450014, Zhengzhou, China.

Henan Gynecological diseases (Gynecology Oncology) Clinical Research Center, 450014, Zhengzhou, China.

出版信息

Sci Rep. 2024 Oct 18;14(1):24469. doi: 10.1038/s41598-024-73601-7.

DOI:10.1038/s41598-024-73601-7
PMID:39424828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11489587/
Abstract

N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIP-qPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy.

摘要

N6-甲基腺苷（m6A）是真核 RNA 中最普遍的修饰，在各种癌症中发挥着重要作用。然而，m6A 修饰影响宫颈癌（CC）发生的机制尚不清楚。因此，我们旨在阐明 METTL3 在 CC 进展中的作用和机制。在本研究中，我们观察到 METTL3 在 CC 组织和细胞系中显著上调。METTL3 敲低导致 CC 细胞的生长、迁移和侵袭减少，并影响细胞凋亡，而过表达 METTL3 则逆转了这些效应。通过对 METTL3 敲低后进行 MeRIP-seq 和 Ribo-seq 联合分析，我们鉴定出 NEK2 是 CC 细胞中 METTL3 的关键靶标。相关性分析、MeRIP-qPCR 和荧光素酶报告基因检测表明，METTL3 通过 m6A 修饰调控 NEK2 的表达。NEK2 与 METTL3 协同作用，介导 CC 细胞的恶性表型。METTL3-NEK2 轴通过激活 Wnt/β-catenin 通路和抑制凋亡通路促进 CC 进展。总之，METTL3 促进了 CC 的恶性进展，并以 m6A 依赖的方式促进了 METTL3-NEK2 调节轴的形成，这代表了 CC 治疗的一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/de01b3ee71a5/41598_2024_73601_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/83511635a3fe/41598_2024_73601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/d6a26bd885e7/41598_2024_73601_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/b3e146613bdf/41598_2024_73601_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/04c1cf11ee08/41598_2024_73601_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/89ce7c216ba3/41598_2024_73601_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/e98e903cfaa0/41598_2024_73601_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/de01b3ee71a5/41598_2024_73601_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/83511635a3fe/41598_2024_73601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/d6a26bd885e7/41598_2024_73601_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/b3e146613bdf/41598_2024_73601_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/04c1cf11ee08/41598_2024_73601_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/89ce7c216ba3/41598_2024_73601_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/e98e903cfaa0/41598_2024_73601_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef35/11489587/de01b3ee71a5/41598_2024_73601_Fig7_HTML.jpg

相似文献

1
METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2.METTL3 通过 m6A 修饰介导的 NEK2 上调促进宫颈癌的进展。
Sci Rep. 2024 Oct 18;14(1):24469. doi: 10.1038/s41598-024-73601-7.
2
M6A-induced transcription factor IRF5 contributes to the progression of cervical cancer by upregulating PPP6C.M6A 诱导的转录因子 IRF5 通过上调 PPP6C 促进宫颈癌的进展。
Clin Exp Pharmacol Physiol. 2024 Jul;51(7):e13868. doi: 10.1111/1440-1681.13868.
3
METTL3 Regulates the Translation of Oncogene Myc through mA Modification and Promotes the Occurrence and Development of Cervical Cancer.METTL3 通过 mA 修饰调控癌基因 Myc 的翻译并促进宫颈癌的发生发展。
Discov Med. 2024 Sep;36(188):1902-1910. doi: 10.24976/Discov.Med.202436188.176.
4
The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1.m6A 甲基转移酶 METTL3 通过调控 LEF1 的 m6A 水平促进骨肉瘤的进展。
Biochem Biophys Res Commun. 2019 Aug 27;516(3):719-725. doi: 10.1016/j.bbrc.2019.06.128. Epub 2019 Jun 26.
5
METTL3-mediated m6A modification of CDCA7 mRNA promotes COAD progression.METTL3 介导的 CDCA7 mRNA m6A 修饰促进结直肠癌进展。
Pathol Res Pract. 2024 Aug;260:155437. doi: 10.1016/j.prp.2024.155437. Epub 2024 Jun 28.
6
Cross talk between RNA N6-methyladenosine methyltransferase-like 3 and miR-186 regulates hepatoblastoma progression through Wnt/β-catenin signalling pathway.RNA N6-甲基腺苷甲基转移酶样 3 与 miR-186 之间的串扰通过 Wnt/β-catenin 信号通路调控肝癌进展。
Cell Prolif. 2020 Mar;53(3):e12768. doi: 10.1111/cpr.12768. Epub 2020 Jan 22.
7
METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA.METTL3 通过调控 TXNDC5 mRNA 的 m6A 修饰抑制内质网应激促进宫颈癌进展。
Oncogene. 2022 Sep;41(39):4420-4432. doi: 10.1038/s41388-022-02435-2. Epub 2022 Aug 20.
8
METTL3's role in cervical cancer development through mA modification.METTL3 通过 mA 修饰在宫颈癌发生发展中的作用。
FASEB J. 2024 Jun 15;38(11):e23693. doi: 10.1096/fj.202400580.
9
METTL3 facilitates prostate cancer progression via inducing HOXC6 m6A modification and stabilizing its expression through IGF2BP2-dependent mechanisms.METTL3 通过诱导 HOXC6 m6A 修饰并通过 IGF2BP2 依赖性机制稳定其表达促进前列腺癌进展。
Mol Cell Biochem. 2024 Jul;479(7):1707-1720. doi: 10.1007/s11010-024-05023-y. Epub 2024 May 31.
10
Mechanism of methyltransferase like 3 in epithelial-mesenchymal transition process, invasion, and metastasis in esophageal cancer.甲基转移酶样蛋白 3 在食管癌上皮-间质转化过程、侵袭和转移中的作用机制。
Bioengineered. 2021 Dec;12(2):10023-10036. doi: 10.1080/21655979.2021.1994721.

引用本文的文献

1
N6-methyladenosine in cervical carcinogenesis: Mechanistic insights and therapeutic perspectives (Review).N6-甲基腺苷在宫颈癌发生中的作用机制及治疗前景（综述）
Oncol Lett. 2025 Jul 14;30(3):442. doi: 10.3892/ol.2025.15188. eCollection 2025 Sep.
2
METTL3 mediates m6A methylation modification of ULBP2 and affects the progression of cervical cancer.METTL3介导ULBP2的m6A甲基化修饰并影响宫颈癌的进展。
Hereditas. 2025 Jul 10;162(1):123. doi: 10.1186/s41065-025-00483-8.

本文引用的文献

1
The roles of m6A methylation in cervical cancer: functions, molecular mechanisms, and clinical applications.m6A 甲基化在宫颈癌中的作用：功能、分子机制及临床应用。
Cell Death Dis. 2023 Nov 11;14(11):734. doi: 10.1038/s41419-023-06265-2.
2
Epigenetic modification of mA regulator proteins in cancer.癌症中 mA 调节蛋白的表观遗传修饰。
Mol Cancer. 2023 Jun 30;22(1):102. doi: 10.1186/s12943-023-01810-1.
3
The evolving landscape of antibody-drug conjugates in gynecologic cancers.妇科癌症中抗体药物偶联物的发展态势
Cancer Treat Rev. 2023 May;116:102546. doi: 10.1016/j.ctrv.2023.102546. Epub 2023 Mar 20.
4
Advances in immunotherapy in cervical cancer.宫颈癌的免疫治疗进展。
Int J Gynecol Cancer. 2023 Mar 6;33(3):403-413. doi: 10.1136/ijgc-2022-003758.
5
ALKBH5 inhibits the SIRT3/ACC1 axis to regulate fatty acid metabolism via an m6A-IGF2BP1-dependent manner in cervical squamous cell carcinoma.在宫颈鳞状细胞癌中，ALKBH5通过一种m6A-IGF2BP1依赖性方式抑制SIRT3/ACC1轴来调节脂肪酸代谢。
Clin Exp Pharmacol Physiol. 2023 May;50(5):380-392. doi: 10.1111/1440-1681.13754. Epub 2023 Feb 18.
6
Top advances of the year: Cervical cancer.年度重大进展：宫颈癌。
Cancer. 2023 Mar 1;129(5):657-663. doi: 10.1002/cncr.34617. Epub 2023 Jan 7.
7
Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative.2020 年全球宫颈癌发病率和死亡率估计：世卫组织全球消除宫颈癌倡议的基线分析。
Lancet Glob Health. 2023 Feb;11(2):e197-e206. doi: 10.1016/S2214-109X(22)00501-0. Epub 2022 Dec 14.
8
YTHDF3 mediates HNF1α regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner.YTHDF3通过以m6A依赖的方式促进RAD51D的翻译来介导HNF1α对宫颈癌放射抗性的调控。
FEBS J. 2023 Apr;290(7):1920-1935. doi: 10.1111/febs.16681. Epub 2022 Dec 15.
9
NEK2 inactivates the Hippo pathway to advance the proliferation of cervical cancer cells by cooperating with STRIPAK complexes.NEK2 通过与 STRIPAK 复合物合作使 Hippo 通路失活，从而促进宫颈癌细胞的增殖。
Cancer Lett. 2022 Nov 28;549:215917. doi: 10.1016/j.canlet.2022.215917. Epub 2022 Sep 14.
10
Recurrent or primary metastatic cervical cancer: current and future treatments.复发性或原发性转移性宫颈癌：当前和未来的治疗方法。
ESMO Open. 2022 Oct;7(5):100579. doi: 10.1016/j.esmoop.2022.100579. Epub 2022 Sep 13.