YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma
YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma
复制标题
YTHDF2 通过破坏肝细胞癌中 EGFR mRNA 的稳定性来抑制细胞增殖和生长。
DOI：
10.1016/j.canlet.2018.11.006
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发表时间：
2019-02-01
期刊：
影响因子：
9.7
通讯作者：
Kang, Tiebang
中科院分区：
文献类型：
--
作者：
Zhong, Li;Liao, Dan;Kang, Tiebang
n -6-甲基腺苷（m(6)A）是真核生物中最普遍的mRNA修饰之一，m(6)A甲基转移酶和去甲基化酶在许多类型的癌症中起着关键作用。然而，m(6) a结合蛋白在癌症中的作用尚不清楚。我们报道了缺氧在肝癌细胞中特异性诱导YTHDF2的下调，并且YTHDF2的过表达抑制了肝癌细胞的增殖、肿瘤生长以及MEK和ERK的激活。在机制上，YTHDF2直接结合EGFR 3'-UTR的m(6)A修饰位点，促进HCC细胞中EGFR mRNA的降解。这是首次报道表明YTHDF2可能作为肿瘤抑制因子，通过破坏HCC中EGFR mRNA的稳定性来抑制细胞增殖和生长。
N-6-methyladenosin (m(6)A) is one of the most pervasive modification of mRNA in eukaryotes and the m(6)A methyltransferases and demethylases play critical roles in many types of cancer. However the role of m(6)A-binding proteins in cancer remains elusive. Here we report that the down-regulation of YTHDF2 was specifically induced by hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression of YTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK in HCC cells. Mechanistically, YTHDF2 directly bound the m(6)A modification site of EGFR 3'-UTR to promote the degradation of EGFR mRNA in HCC cells. This is the first report showing that YTHDF2 may act as a tumor suppressor to repress cell proliferation and growth via destabilizing the EGFR mRNA in HCC.