YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner.
YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner.
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DOI：
10.1016/j.omtn.2020.09.036
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Liu X;Qin J;Gao T;Li C;He B;Pan B;Xu X;Chen X;Zeng K;Xu M;Zhu C;Pan Y;Sun H;Sun L;Xu T;Wang S
肝细胞癌（HCC）是最具侵袭性的恶性肿瘤之一，在全世界范围内是癌症相关死亡的第四大原因。新出现的证据表明，RNA N6-甲基腺苷（m6 A）在肿瘤进展中起着关键作用。然而，YTHDF 1在HCC中的生物学功能尚不清楚。在这里，我们发现YTHDF 1表达在HCC组织和细胞系中显著升高，并且与HCC患者的预后显著相关。此外，YTHDF 1的表达在HCC中受USF 1和c-MYC的转录调控。功能研究表明，YTHDF 1在体外和体内均可促进肝癌细胞增殖和转移。多组学分析显示YTHDF 1可以以m6 A依赖的方式加速FZD 5 mRNA的翻译输出，并通过WNT/β-catenin途径作为癌基因发挥作用。综上所述，我们的研究揭示了YTHDF 1在HCC细胞的发展中的重要作用，这表明靶向YTHDF 1可能是HCC的潜在治疗策略。N6-甲基腺苷在肿瘤进展中起关键作用。Liu等人证明了YTHDF 1（N6-甲基腺苷阅读器）在肝细胞癌中的表达和调控机制，这表明靶向YTHDF 1可能是肝细胞癌的潜在治疗策略。
Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/β-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC. N6-methyladenosine plays a critical role in tumor progression. Liu et al. demonstrate the expression and regulatory mechanisms of YTHDF1, an N6-methyladenosine reader, in hepatocellular carcinoma, which suggests targeting YTHDF1 may be a potential therapeutic strategy in hepatocellular carcinoma.
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影响因子：
16.6
作者：
Du, Hao;Zhao, Ya;He, Jinqiu;Zhang, Yao;Xi, Hairui;Liu, Mofang;Ma, Jinbiao;Wu, Ligang
通讯作者：
Wu, Ligang
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影响因子：
37.3
作者：
Liu, Li;Wang, Jing;Pan, Qiuhui
通讯作者：
Pan, Qiuhui
影响因子：
64.5
作者：
Meyer KD;Patil DP;Zhou J;Zinoviev A;Skabkin MA;Elemento O;Pestova TV;Qian SB;Jaffrey SR
通讯作者：
Jaffrey SR
DOI：
10.1002/hep.27923
发表时间：
2015-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Lu Y;Xu W;Ji J;Feng D;Sourbier C;Yang Y;Qu J;Zeng Z;Wang C;Chang X;Chen Y;Mishra A;Xu M;Lee MJ;Lee S;Trepel J;Linehan WM;Wang X;Yang Y;Neckers L
通讯作者：
Neckers L
影响因子：
14.9
作者：
Caggiano, Cinzia;Pieraccioli, Marco;Bielli, Pamela
通讯作者：
Bielli, Pamela