• 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

mA 修饰通过调节 HINT2 mRNA 翻译抑制眼黑色素瘤。

mA modification suppresses ocular melanoma through modulating HINT2 mRNA translation.

机构信息

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 20025, People's Republic of China.

Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 20025, People's Republic of China.

出版信息

Mol Cancer. 2019 Nov 14;18(1):161. doi: 10.1186/s12943-019-1088-x.

DOI:10.1186/s12943-019-1088-x
PMID:31722709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6854757/
Abstract

BACKGROUND

Dynamic N-methyladenosine (mA) RNA modification generated and erased by N-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal melanoma (UM) and conjunctival melanoma (CM), is the most common primary eye tumor in adults and the 2nd most common melanoma. However, the functional role of mA modification in ocular melanoma remains unclear.

METHODS

mA assays and survival analysis were used to explore decreased global mA levels, indicating a late stage of ocular melanoma and a poor prognosis. Multiomic analysis of miCLIP-seq, RNA-seq and Label-free MS data revealed that mA RNA modification posttranscriptionally promoted HINT2 expression. RNA immunoprecipitation (RIP)-qPCR and dual luciferase assays revealed that HINT2 mRNA specifically interacted with YTHDF1. Furthermore, polysome profiling analysis indicated a greater amount of HINT2 mRNA in the translation pool in ocular melanoma cells with higher mA methylation.

RESULTS

Here, we show that RNA methylation significantly inhibits the progression of UM and CM. Ocular melanoma samples showed decreased mA levels, indicating a poor prognosis. Changes in global mA modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of methylated HINT2 mRNA, a tumor suppressor in ocular melanoma.

CONCLUSIONS

Our work uncovers a critical function for mA methylation in ocular melanoma and provides additional insight into the understanding of mA modification.

摘要

背景

动态 N6-甲基腺苷（mA）RNA 修饰由 N 甲基转移酶和去甲基酶产生和消除，调节基因表达、选择性剪接和细胞命运。眼黑素瘤包括葡萄膜黑素瘤（UM）和结膜黑素瘤（CM），是成人中最常见的原发性眼部肿瘤，也是第二常见的黑素瘤。然而，mA 修饰在眼黑素瘤中的功能作用尚不清楚。

方法

mA 分析和生存分析用于探索降低的全局 mA 水平，表明眼黑素瘤处于晚期且预后不良。miCLIP-seq、RNA-seq 和无标记 MS 数据的多组学分析显示，mA RNA 修饰在后转录水平促进 HINT2 的表达。RNA 免疫沉淀（RIP）-qPCR 和双荧光素酶测定显示 HINT2 mRNA 与 YTHDF1 特异性相互作用。此外，多核糖体分析表明在具有更高 mA 甲基化的眼黑素瘤细胞中，HINT2 mRNA 更多地存在于翻译池中。

结果

在这里，我们表明 RNA 甲基化显著抑制 UM 和 CM 的进展。眼黑素瘤样本显示 mA 水平降低，预示预后不良。全局 mA 修饰的变化与体外和体内肿瘤进展高度相关。机制上，YTHDF1 促进了 HINT2 mRNA 的翻译，HINT2 mRNA 是眼黑素瘤中的一种肿瘤抑制因子。

结论

我们的工作揭示了 mA 甲基化在眼黑素瘤中的关键功能，并为理解 mA 修饰提供了更多的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/ab897b9005bb/12943_2019_1088_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/51a31f49272f/12943_2019_1088_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/a84c2edc7225/12943_2019_1088_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/8f0b6a564f6c/12943_2019_1088_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/630a545733a2/12943_2019_1088_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/20daf2117f1b/12943_2019_1088_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/f1c489720ec9/12943_2019_1088_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/ab897b9005bb/12943_2019_1088_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/51a31f49272f/12943_2019_1088_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/a84c2edc7225/12943_2019_1088_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/8f0b6a564f6c/12943_2019_1088_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/630a545733a2/12943_2019_1088_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/20daf2117f1b/12943_2019_1088_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/f1c489720ec9/12943_2019_1088_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aef3/6854757/ab897b9005bb/12943_2019_1088_Fig7_HTML.jpg

相似文献

1
mA modification suppresses ocular melanoma through modulating HINT2 mRNA translation.mA 修饰通过调节 HINT2 mRNA 翻译抑制眼黑色素瘤。
Mol Cancer. 2019 Nov 14;18(1):161. doi: 10.1186/s12943-019-1088-x.
2
Histone lactylation drives oncogenesis by facilitating mA reader protein YTHDF2 expression in ocular melanoma.组蛋白乳酰化通过促进眼黑色素瘤中 mA 读码蛋白 YTHDF2 的表达来驱动肿瘤发生。
Genome Biol. 2021 Mar 16;22(1):85. doi: 10.1186/s13059-021-02308-z.
3
The mA reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation.mA 阅读蛋白 YTHDF3 通过促进 CTNNB1 翻译增强眼黑色素瘤中肿瘤干细胞样细胞的致瘤性。
Oncogene. 2022 Feb;41(9):1281-1297. doi: 10.1038/s41388-021-02146-0. Epub 2022 Feb 3.
4
mA RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.mA RNA 高甲基化诱导的 BACE2 促进细胞内钙释放并加速眼黑色素瘤的肿瘤发生。
Mol Ther. 2021 Jun 2;29(6):2121-2133. doi: 10.1016/j.ymthe.2021.02.014. Epub 2021 Feb 15.
5
RNA m A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met.RNA mA 甲基化通过靶向 c-Met 调节葡萄膜黑色素瘤细胞的增殖、迁移和侵袭。
J Cell Physiol. 2020 Oct;235(10):7107-7119. doi: 10.1002/jcp.29608. Epub 2020 Feb 4.
6
Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified m A RNA methylation in ocular melanoma.靶向组蛋白去乙酰化酶通过诱导眼黑素瘤中 METTL14 修饰的 mA RNA 甲基化抑制肿瘤生长。
Cancer Commun (Lond). 2023 Nov;43(11):1185-1206. doi: 10.1002/cac2.12471. Epub 2023 Jul 19.
7
Physio-pathological effects of m6A modification and its potential contribution to melanoma.m6A 修饰的生理病理效应及其对黑色素瘤的潜在贡献。
Clin Transl Oncol. 2021 Nov;23(11):2269-2279. doi: 10.1007/s12094-021-02644-3. Epub 2021 Jun 8.
8
YTHDF1-enhanced iron metabolism depends on TFRC mA methylation.YTHDF1 增强的铁代谢依赖于 TFRC 的 mA 甲基化。
Theranostics. 2020 Oct 26;10(26):12072-12089. doi: 10.7150/thno.51231. eCollection 2020.
9
METTL3 Promotes Tumorigenesis and Metastasis through BMI1 mA Methylation in Oral Squamous Cell Carcinoma.METTL3 通过 BMI1 的 mA 甲基化促进口腔鳞状细胞癌的发生和转移。
Mol Ther. 2020 Oct 7;28(10):2177-2190. doi: 10.1016/j.ymthe.2020.06.024. Epub 2020 Jun 24.
10
ZNF677 suppresses renal cell carcinoma progression through N6-methyladenosine and transcriptional repression of CDKN3.ZNF677 通过 N6-甲基腺苷和转录抑制 CDKN3 抑制肾细胞癌进展。
Clin Transl Med. 2022 Jun;12(6):e906. doi: 10.1002/ctm2.906.

引用本文的文献

1
RNA mA modification: a key regulator in normal and malignant processes.RNA mA修饰：正常和恶性过程中的关键调节因子。
Cell Investig. 2025 Jun;1(2). doi: 10.1016/j.clnves.2025.100023. Epub 2025 Jun 6.
2
Dual roles of N-methyladenosine in R-loop regulation of gene transcription and genome stability.N-甲基腺苷在基因转录的R环调控和基因组稳定性中的双重作用。
Sci China Life Sci. 2025 Jul 9. doi: 10.1007/s11427-024-2947-6.
3
circNRIP1 impairs tumorigenesis of colorectal cancer by sponging IGF2BP1 and decreasing mRNA stability.环状核糖核酸NRIP1通过吸附IGF2BP1并降低mRNA稳定性来损害结直肠癌的肿瘤发生。

本文引用的文献

1
Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway.上调的 METTL3 通过 miR-1246/SPRED2/MAPK 信号通路促进结直肠癌的转移。
J Exp Clin Cancer Res. 2019 Sep 6;38(1):393. doi: 10.1186/s13046-019-1408-4.
2
Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K-Akt signaling in gastric cancer.m6A 修饰降低预示着胃癌的恶性表型，并增强了 Wnt/PI3K-Akt 信号通路。
Cancer Med. 2019 Aug;8(10):4766-4781. doi: 10.1002/cam4.2360. Epub 2019 Jun 26.
3
Excessive miR-25-3p maturation via N-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression.
Gastroenterol Rep (Oxf). 2025 Jun 20;13:goaf041. doi: 10.1093/gastro/goaf041. eCollection 2025.
4
Chemically modified non-coding RNAs in cancer.癌症中的化学修饰非编码RNA
Expert Rev Mol Med. 2025 Jun 9;27:e19. doi: 10.1017/erm.2025.10007.
5
RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.RNA表观遗传修饰作为癌症中的动态生物标志物：从机制到临床转化
Biomark Res. 2025 Jun 7;13(1):81. doi: 10.1186/s40364-025-00794-y.
6
PSMB10 maintains the stemness of chemotherapeutic drug-resistant leukemia cells by inhibiting senescence and cytotoxic T lymphocyte-mediated killing in a ubiquitinated degradation manner.蛋白酶体亚基β型10通过以泛素化降解的方式抑制衰老和细胞毒性T淋巴细胞介导的杀伤作用，维持化疗耐药白血病细胞的干性。
J Exp Clin Cancer Res. 2025 Jun 3;44(1):170. doi: 10.1186/s13046-025-03420-9.
7
Histidine triad nucleotide-binding protein 2 attenuates metabolic dysfunction-associated steatotic liver disease through NAD-dependent sirtuin-3 activation.组氨酸三联体核苷酸结合蛋白2通过烟酰胺腺嘌呤二核苷酸（NAD）依赖的沉默调节蛋白3激活减轻代谢功能障碍相关脂肪性肝病。
Exp Mol Med. 2025 May 1. doi: 10.1038/s12276-025-01445-w.
8
YTHDF1/RNF7/p27 axis promotes prostate cancer progression.YTHDF1/RNF7/p27轴促进前列腺癌进展。
Cell Death Dis. 2025 Apr 18;16(1):314. doi: 10.1038/s41419-025-07648-3.
9
Targeting mA RNA Modification in Tumor Therapeutics.肿瘤治疗中针对 mA RNA 修饰
Curr Oncol. 2025 Mar 11;32(3):159. doi: 10.3390/curroncol32030159.
10
METTL3 mediates CPB1 expression by regulating transcription factor BACH2 to promote apoptosis and oxidative stress of lens epithelial cells.METTL3通过调节转录因子BACH2介导CPB1表达，以促进晶状体上皮细胞的凋亡和氧化应激。
J Bioenerg Biomembr. 2025 Feb 21. doi: 10.1007/s10863-025-10054-1.
吸烟刺激 N6-甲基腺苷促进 miR-25-3p 成熟从而促进胰腺癌进展。
Nat Commun. 2019 Apr 23;10(1):1858. doi: 10.1038/s41467-019-09712-x.
4
ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.ALKBH5 通过 miR-7 和 BCL-2 抑制上皮性卵巢癌细胞自噬。
J Exp Clin Cancer Res. 2019 Apr 15;38(1):163. doi: 10.1186/s13046-019-1159-2.
5
-Methyladenosine modification: a novel pharmacological target for anti-cancer drug development.N6-甲基腺苷修饰：抗癌药物研发的新型药理学靶点。
Acta Pharm Sin B. 2018 Oct;8(6):833-843. doi: 10.1016/j.apsb.2018.06.001. Epub 2018 Jun 6.
6
[GSA: Genome Sequence Archive].[GSA：基因组序列档案库]
Yi Chuan. 2018 Nov 20;40(11):1044-1047. doi: 10.16288/j.yczz.18-178.
7
METTL3-mediated N-methyladenosine mRNA modification enhances long-term memory consolidation.METTL3 介导的 N6-甲基腺苷 mRNA 修饰增强长时程记忆巩固。
Cell Res. 2018 Nov;28(11):1050-1061. doi: 10.1038/s41422-018-0092-9. Epub 2018 Oct 8.
8
mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis.METTL3-eIF3h 通过 mRNA 环化增强翻译并促进致癌作用。
Nature. 2018 Sep;561(7724):556-560. doi: 10.1038/s41586-018-0538-8. Epub 2018 Sep 19.
9
mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer.mA mRNA 甲基化调节 AKT 活性，促进子宫内膜癌的增殖和致瘤性。
Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
10
Novel insights on mA RNA methylation in tumorigenesis: a double-edged sword.新型肿瘤发生中 mA RNA 甲基化的见解：一把双刃剑。
Mol Cancer. 2018 Jul 21;17(1):101. doi: 10.1186/s12943-018-0847-4.