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YTHDF1调节人类结直肠癌的致瘤性和癌症干细胞样活性。

YTHDF1 Regulates Tumorigenicity and Cancer Stem Cell-Like Activity in Human Colorectal Carcinoma.

作者信息

Bai Yang, Yang Chunxing, Wu Runliu, Huang Lihua, Song Shenlei, Li Wanwan, Yan Peichen, Lin Changwei, Li Daojiang, Zhang Yi

机构信息

Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.

Center for Medical Experiments, The Third Xiangya Hospital of Central South University, Changsha, China.

出版信息

Front Oncol. 2019 May 3;9:332. doi: 10.3389/fonc.2019.00332. eCollection 2019.

Abstract

YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) is a core factor in RNA methylation modification. Recent studies have shown that m6A is closely related to multiple tumors, thus YTHDF1 may also play a role in tumorigenesis. This study, aimed to explore the role of YTHDF1 in the colorectal cancer (CRC). In this study, we identified YTHDF1 as being highly expressed at the mRNA and protein levels in TCGA, GEO CRC and primary CRC. Furthermore, the YTHDF1 gene copy number was positively correlated with YTHDF1 mRNA expression in CRC. Knocking down the expression of YTHDF1 significantly inhibited the CRC cell's tumorigenicity and murine xenograft tumor growth . Furthermore, silencing of YTHDF1 inhibited the colonosphere formation ability . Mechanistically, we found that silencing YTHDF1 significantly inhibited Wnt/β-catenin pathway activity in CRC cells. Together, YTHDF1 is overexpressed in CRC and plays a vital oncogenic role in CRC, and this novel finding may provide a potential therapeutic target for CRC.

摘要

YTH N6-甲基腺苷(m6A)RNA结合蛋白1(YTHDF1)是RNA甲基化修饰中的一个核心因子。最近的研究表明,m6A与多种肿瘤密切相关,因此YTHDF1可能也在肿瘤发生过程中发挥作用。本研究旨在探讨YTHDF1在结直肠癌(CRC)中的作用。在本研究中,我们发现在TCGA、GEO CRC数据集以及原发性CRC中,YTHDF1在mRNA和蛋白水平均高表达。此外,在CRC中YTHDF1基因拷贝数与YTHDF1 mRNA表达呈正相关。敲低YTHDF1的表达显著抑制了CRC细胞的致瘤性以及小鼠异种移植瘤的生长。此外,沉默YTHDF1抑制了结肠球形成能力。机制上,我们发现沉默YTHDF1显著抑制了CRC细胞中Wnt/β-连环蛋白信号通路的活性。总之,YTHDF1在CRC中过表达并在CRC中发挥重要的致癌作用,这一新发现可能为CRC提供一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a8b/6509179/4f79778abee8/fonc-09-00332-g0001.jpg

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