YTHDF1 Regulates Tumorigenicity and Cancer Stem Cell-Like Activity in Human Colorectal Carcinoma
YTHDF1 Regulates Tumorigenicity and Cancer Stem Cell-Like Activity in Human Colorectal Carcinoma
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DOI：
10.3389/fonc.2019.00332
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发表时间：
2019-05-03
影响因子：
4.7
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Bai, Yang;Yang, Chunxing;Zhang, Yi
YTH N6-甲基腺苷（m6 A）RNA结合蛋白1（YTHDF 1）是RNA甲基化修饰的核心因子。最近的研究表明，m6 A与多种肿瘤密切相关，因此YTHDF 1也可能在肿瘤发生中发挥作用。本研究旨在探讨YTHDF 1在结直肠癌中的作用。在这项研究中，我们确定YTHDF 1在TCGA，GEO CRC和原发性CRC中在mRNA和蛋白水平上高度表达。结直肠癌中YTHDF 1基因拷贝数与YTHDF 1 mRNA表达呈正相关。敲低YTHDF 1的表达显著抑制CRC细胞的体外致瘤性和小鼠异种移植瘤的体内生长。此外，YTHDF 1的沉默抑制体外结肠球形成能力。从机制上讲，我们发现沉默YTHDF 1显著抑制CRC细胞中的Wnt/β-连环蛋白通路活性。总之，YTHDF 1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提供潜在的治疗靶点。
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 in vitro and murine xenograft tumor growth in vivo. Furthermore, silencing of YTHDF1 inhibited the colonosphere formation ability in vitro. Mechanistically, we found that silencing YTHDF1 significantly inhibited Wnt/beta-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.