YTHDF1通过激活PI3K/AKT/mTOR信号通路和诱导上皮-间质转化促进肝细胞癌进展。

YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition.

作者信息

Luo Xiangyuan, Cao Mengdie, Gao Fan, He Xingxing

机构信息

Institute of Liver and Gastrointestinal Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

Exp Hematol Oncol. 2021 Jun 4;10(1):35. doi: 10.1186/s40164-021-00227-0.

BACKGROUND

N-methyladenosine (mA) modification, as the most abundant RNA modification, widely participates in the physiological process and is involved in multiple disease progression, especially cancer. YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) is a pivotal mA "reader" protein, which has been reported in multiple cancers. However, the role and molecular mechanism of YTHDF1 in HCC are still not fully elucidated.

METHODS

Based on various bioinformatics databases, q-RT PCR, western blot, and a tissue microarray containing 90 HCC samples, we examined the expression of YTHDF1 in HCC. Then, we applied the loss-of-function experiments to explore the role of YTHDF1 in HCC by in vitro and in vivo assays. Finally, we performed the gene set enrichment analysis (GSEA) to predict the potential signaling pathway of YTHDF1 involved in HCC and further verified this prediction.

RESULTS

YTHDF1 was overexpressed in HCC and associated with HCC grade. Depletion of YTHDF1 markedly impaired the proliferation, migration, invasion, and cell cycle process of HCC cells. Mechanistically, YTHDF1 promoted the growth of HCC cells via activating the PI3K/AKT/mTOR signaling pathway. Moreover, we also demonstrated that the epithelial-mesenchymal transition (EMT) mediated the promoting effect of YTHDF1 on the migration and invasion of HCC cells.

CONCLUSIONS

YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/mTOR signaling pathway and inducing EMT.

背景

N-甲基腺苷（mA）修饰作为最丰富的RNA修饰，广泛参与生理过程，并涉及多种疾病进展，尤其是癌症。YTH N6-甲基腺苷RNA结合蛋白1（YTHDF1）是一种关键的mA“读取器”蛋白，已在多种癌症中报道。然而，YTHDF1在肝癌中的作用和分子机制仍未完全阐明。

方法

基于各种生物信息学数据库、q-RT PCR、蛋白质印迹法以及包含90个肝癌样本的组织芯片，我们检测了YTHDF1在肝癌中的表达。然后，我们应用功能丧失实验，通过体外和体内实验来探究YTHDF1在肝癌中的作用。最后，我们进行基因集富集分析（GSEA）以预测YTHDF1参与肝癌的潜在信号通路，并进一步验证这一预测。