Suppr超能文献

m6A RNA 甲基化调控因子在卵巢癌中的基因特征和预后价值。

Gene Signatures and Prognostic Values of m6A RNA Methylation Regulators in Ovarian Cancer.

机构信息

Department of Obstetrics and Gynecology, 117977The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Internal Medicine, 117977The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Cancer Control. 2020 Jan-Dec;27(1):1073274820960460. doi: 10.1177/1073274820960460.

Abstract

BACKGROUND

N6-methyladenosine (m6A) is the most common form of mRNA modification under the field of "RNA epigenetics." However, its role in ovarian cancer (OC) development is poorly understood. In the current study, we aimed to identify gene signatures and prognostic values of m6A RNA methylation regulators.

METHOD

Specifically, we downloaded Mutations and Copy number variant (CNV) data from the TCGA database for 579 OC patients, then analyzed gene expression and prognosis value using integrative bioinformatics. Thereafter, we verified the related biological processes of Wilms' tumor 1-associating protein (WTAP) gene using Gene set enrichment analysis (GSEA).

RESULTS

Results showed that almost all ovarian cancer patients (99.31%) have CNVs with at least 1 m6A regulatory gene, whereas 83.76% of cases exhibited concurrence of CNVs in more than 4 m6A regulatory genes. Additionally, alteration of m6A regulators was associated with historical grade, whereas integrative bioinformatics and Cox multivariate model analysis revealed a significant correlation between high WTAP expression and worse ovarian cancer outcomes. Moreover, GSEA revealed that high WTAP expression was associated with cell cycle regulation and MYC targets.

CONCLUSION

Overall, our findings demonstrate the significance of high-frequency genetic alterations of m6A RNA methylation regulators and WTAP's poor prognosis value in OC. These findings provide valuable insights into the role of m6A methylation in OC, and will be vital in guiding development of novel treatment therapies.

摘要

背景

N6-甲基腺苷(m6A)是“RNA 表观遗传学”领域中最常见的 mRNA 修饰形式。然而,其在卵巢癌(OC)发展中的作用尚不清楚。在本研究中,我们旨在确定 m6A RNA 甲基化调节剂的基因特征和预后价值。

方法

具体来说,我们从 TCGA 数据库下载了 579 名 OC 患者的突变和拷贝数变异(CNV)数据,然后使用整合生物信息学方法分析基因表达和预后值。之后,我们使用基因集富集分析(GSEA)验证了Wilms 肿瘤 1 相关蛋白(WTAP)基因的相关生物学过程。

结果

结果表明,几乎所有卵巢癌患者(99.31%)的 CNVs 都至少有 1 个 m6A 调节基因,而 83.76%的病例表现出超过 4 个 m6A 调节基因的 CNVs 同时发生。此外,m6A 调节剂的改变与历史分级有关,而整合生物信息学和 Cox 多变量模型分析表明,WTAP 高表达与卵巢癌结局较差显著相关。此外,GSEA 表明,WTAP 高表达与细胞周期调控和 MYC 靶标有关。

结论

总体而言,我们的研究结果表明,m6A RNA 甲基化调节剂的高频遗传改变和 WTAP 预后不良在 OC 中具有重要意义。这些发现为 m6A 甲基化在 OC 中的作用提供了有价值的见解,并将对指导新型治疗方法的发展具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd1d/7791456/fdcdfad5acfb/10.1177_1073274820960460-fig1.jpg

相似文献

1
Gene Signatures and Prognostic Values of m6A RNA Methylation Regulators in Ovarian Cancer.
Cancer Control. 2020 Jan-Dec;27(1):1073274820960460. doi: 10.1177/1073274820960460.
2
N6-Methyladenosine-Related RNA Signature Predicting the Prognosis of Ovarian Cancer.
Recent Pat Anticancer Drug Discov. 2021;16(3):407-416. doi: 10.2174/1574892816666210615164645.
3
High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates mA methylation of MYC mRNA.
J Cancer Res Clin Oncol. 2021 Jan;147(1):33-47. doi: 10.1007/s00432-020-03373-w. Epub 2020 Sep 3.
5
m6A RNA methylation regulators were associated with the malignancy and prognosis of ovarian cancer.
Bioengineered. 2021 Dec;12(1):3159-3176. doi: 10.1080/21655979.2021.1946305.
7
METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP.
Cell Biol Int. 2020 Dec;44(12):2524-2531. doi: 10.1002/cbin.11459. Epub 2020 Sep 11.
8
High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour-associated T lymphocyte infiltration.
J Cell Mol Med. 2020 Apr;24(8):4452-4465. doi: 10.1111/jcmm.15104. Epub 2020 Mar 16.
9
Gene Alterations of N6-Methyladenosine (mA) Regulators in Colorectal Cancer: A TCGA Database Study.
Biomed Res Int. 2020 Dec 19;2020:8826456. doi: 10.1155/2020/8826456. eCollection 2020.
10

引用本文的文献

1
Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health.
Cell Death Discov. 2025 Feb 4;11(1):43. doi: 10.1038/s41420-025-02324-z.
2
Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer.
Cancer Control. 2024 Jan-Dec;31:10732748241256819. doi: 10.1177/10732748241256819.
3
Emerging role of m6A modification in ovarian cancer: progression, drug resistance, and therapeutic prospects.
Front Oncol. 2024 Mar 13;14:1366223. doi: 10.3389/fonc.2024.1366223. eCollection 2024.
4
The potential regulatory role of RNA methylation in ovarian cancer.
RNA Biol. 2023 Jan;20(1):207-218. doi: 10.1080/15476286.2023.2213915.
5
Roles of N-methyladenosine (mA) modifications in gynecologic cancers: mechanisms and therapeutic targeting.
Exp Hematol Oncol. 2022 Nov 12;11(1):98. doi: 10.1186/s40164-022-00357-z.
6
Effects of N-Methyladenosine Modification on Cancer Progression: Molecular Mechanisms and Cancer Therapy.
Front Oncol. 2022 May 30;12:897895. doi: 10.3389/fonc.2022.897895. eCollection 2022.
7
A Panel of E2F Target Gene Signature Predicting the Prognosis of Hepatocellular Carcinoma.
Front Genet. 2022 May 3;13:879299. doi: 10.3389/fgene.2022.879299. eCollection 2022.
9
Emerging Roles of mA RNA Methylation Regulators in Gynecological Cancer.
Front Oncol. 2022 Jan 28;12:827956. doi: 10.3389/fonc.2022.827956. eCollection 2022.
10
RNA m6A methylation regulators in ovarian cancer.
Cancer Cell Int. 2021 Nov 18;21(1):609. doi: 10.1186/s12935-021-02318-8.

本文引用的文献

1
WTAP is a prognostic marker of high-grade serous ovarian cancer and regulates the progression of ovarian cancer cells.
Onco Targets Ther. 2019 Aug 6;12:6191-6201. doi: 10.2147/OTT.S205730. eCollection 2019.
3
Relationship between the genetic expression of WTAP and bladder cancer and patient prognosis.
Oncol Lett. 2018 Dec;16(6):6966-6970. doi: 10.3892/ol.2018.9554. Epub 2018 Oct 5.
4
Methylation of Structured RNA by the mA Writer METTL16 Is Essential for Mouse Embryonic Development.
Mol Cell. 2018 Sep 20;71(6):986-1000.e11. doi: 10.1016/j.molcel.2018.08.004. Epub 2018 Sep 6.
5
mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer.
Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
6
The Role of mA/m-RNA Methylation in Stress Response Regulation.
Neuron. 2018 Jul 25;99(2):389-403.e9. doi: 10.1016/j.neuron.2018.07.009.
7
Novel insights on mA RNA methylation in tumorigenesis: a double-edged sword.
Mol Cancer. 2018 Jul 21;17(1):101. doi: 10.1186/s12943-018-0847-4.
8
mA RNA Methylation Controls Neural Development and Is Involved in Human Diseases.
Mol Neurobiol. 2019 Mar;56(3):1596-1606. doi: 10.1007/s12035-018-1138-1. Epub 2018 Jun 16.
9
mA demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.
Biochem Biophys Res Commun. 2018 Aug 25;502(4):456-464. doi: 10.1016/j.bbrc.2018.05.175. Epub 2018 Jun 2.
10
RNA N-methyladenosine modification in cancers: current status and perspectives.
Cell Res. 2018 May;28(5):507-517. doi: 10.1038/s41422-018-0034-6. Epub 2018 Apr 23.

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

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验