YTHDF1 Aggravates the Progression of Cervical Cancer Through m(6)A-Mediated Up-Regulation of RANBP2.
YTHDF1 Aggravates the Progression of Cervical Cancer Through m(6)A-Mediated Up-Regulation of RANBP2.
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YTHDF1 通过 m6A 介导的 RANBP2 上调加剧宫颈癌的进展
DOI：
10.3389/fonc.2021.650383
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yi P
中科院分区：
文献类型：
--
作者：
Wang H;Luo Q;Kang J;Wei Q;Yang Y;Yang D;Liu X;Liu T;Yi P
N6-甲基腺苷（m6 A）是真核生物中最常见的RNA转录后修饰，已被证明在多种癌症中发挥重要作用。YTHDF 1作为一个关键的m6 A“阅读器”，并调节m6 A修饰的mRNA的命运。然而，它在宫颈癌中的作用仍然未知。在本研究中，我们发现YTHDF 1在宫颈癌中高表达，并且与宫颈癌患者的不良预后密切相关。YTHDF 1基因敲低可抑制宫颈癌细胞的生长、迁移和侵袭，并诱导细胞凋亡。此外，YTHDF 1敲低抑制体内宫颈癌细胞的肿瘤发生。通过对RIP-seq、meRIP-seq和Ribo-seq在YTHDF 1敲低后的组合在线数据分析，RANBP 2被鉴定为YTHDF 1在宫颈癌细胞中的关键靶点。YTHDF 1以m6 A依赖的方式调节RANBP 2的翻译，而不影响其mRNA表达。RANBP 2增强宫颈癌细胞的生长、迁移和侵袭。我们的研究表明YTHDF 1通过调节RANBP 2表达在宫颈癌中发挥致癌作用，YTHDF 1代表了宫颈癌治疗的潜在靶点。
N6-methyladenosine (m6A) is the most common post-transcriptional modification of RNA in eukaryotes, which has been demonstrated to play important roles in various cancers. YTHDF1 acts as a crucial m6A “reader” and regulates the fate of m6A modified mRNA. However, its role in cervical cancer remains unknown. In this study, we showed that YTHDF1 was highly expressed in cervical cancer, and was closely associated with the poor prognosis of cervical cancer patients. YTHDF1 knockdown suppressed the growth, migration and invasion, and induced apoptosis of cervical cancer cells. Moreover, YTHDF1 knockdown inhibited tumorigenesis of cervical cancer cells in vivo. Through combined on-line data analysis of RIP-seq, meRIP-seq and Ribo-seq upon YTHDF1 knockdown, RANBP2 was identified as the key target of YTHDF1 in cervical cancer cells. YTHDF1 regulated RANBP2 translation in an m6A-dependent manner without effect on its mRNA expression. RANBP2 potentiated the growth, migration and invasion of cervical cancer cells. Our study demonstrated the oncogenic role of YTHDF1 in cervical cancer by regulating RANBP2 expression and YTHDF1 represents a potential target for cervical cancer therapy.
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影响因子：
4.6
作者：
Lesbirel S;Viphakone N;Parker M;Parker J;Heath C;Sudbery I;Wilson SA
通讯作者：
Wilson SA
影响因子：
50.3
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3.3
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Hutten, Saskia;Flotho, Annette;Kehlenbach, Ralph H.
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Kehlenbach, Ralph H.
影响因子：
50.3
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Schnepp RW;Khurana P;Attiyeh EF;Raman P;Chodosh SE;Oldridge DA;Gagliardi ME;Conkrite KL;Asgharzadeh S;Seeger RC;Madison BB;Rustgi AK;Maris JM;Diskin SJ
通讯作者：
Diskin SJ
影响因子：
64.5
作者：
Roundtree IA;Evans ME;Pan T;He C
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He C