YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway.
YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway.
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DOI：
10.3389/fgene.2020.592042
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发表时间：
2020
影响因子：
3.7
通讯作者：
Zhuang Z
中科院分区：
文献类型：
--
作者：
Shen X;Zhao K;Xu L;Cheng G;Zhu J;Gan L;Wu Y;Zhuang Z
胃癌是世界上最常见的恶性肿瘤之一，也是全球第四大常见恶性肿瘤。YTHDF2(YTH结构域家族2，YTHDF2)与含有m6A的信使核糖核酸结合，从而调节结合信使核糖核酸的定位和稳定性。YTHDF2与某些癌症患者的预后有关。然而，YTHDF2对胃癌的作用及其分子机制尚未见文献报道。为了进行这项研究，我们分析了YTHDF2在公共数据库和胃癌患者样本中的表达水平。体内和体外检测YTHDF2对胃癌细胞生长的影响。用RNA-SEQ分析YTHDF2调控的信号通路，并进行实验验证。在我们的研究中，我们发现YTHDF2在GC组织和GC细胞中的表达水平较低，并抑制了GC细胞的生长。此外，通过对临床资料的分析发现，YTHDF2的表达水平与胃癌的分期和患者的生存密切相关。RNA测序结果表明，YTHDF2过表达显著降低了FOXC2(Forkhead box Protein C2，FOXC2)信号通路中的蛋白表达。最后，我们发现FOXC2基因的敲除逆转了YTHDF2对GC细胞的抑制作用。综上所述，YTHDF2通过负性调控FOXC2抑制GC细胞的生长，可作为GC预后的标志物。
Gastric cancer (GC) is one of the most common malignancies in the world, and the fourth most frequent malignancy worldwide. YTHDF2 (YTH domain family 2, YTHDF2) binds to mRNA containing m6A, thereby regulating the localization and stability of the bound mRNA. YTHDF2 was shown to be associated with some cancer patient prognosis. However, the effect of YTHDF2 on gastric cancer and the molecular mechanism of this effect have not been documented. To conduct this research, YTHDF2 expression levels in public databases and gastric cancer patient samples were analyzed. The effects of YTHDF2 on the growth of gastric cancer cells were detected in vivo and in vitro. RNA-seq was used to analyze the signal pathways regulated by YTHDF2, and experiments were carried out for verification. In our study, we found that YTHDF2 has lower expression in GC tissues and GC cells, and inhibits the growth of GC cells. In addition, the analysis of clinical data found that the expression level of YTHDF2 is closely related to the stage of GC and the survival of patients with GC. RNA sequencing results showed that overexpression of YTHDF2 significantly reduced protein expression in the FOXC2 (Forkhead box protein C2, FOXC2) signaling pathway. Finally, we found that knockout of FOXC2 reversed the inhibitory effect of YTHDF2 on GC cells. In summary, YTHDF2 inhibits the growth of GC cells by negatively regulating FOXC2 and may serve as a prognostic marker in GC.