甲基化
蛋白激酶B
癌症研究
生物
调节器
PI3K/AKT/mTOR通路
RNA甲基化
子宫内膜癌
DNA甲基化
细胞生长
细胞生物学
甲基转移酶
磷酸化
癌症
基因表达
信号转导
基因
遗传学
作者
Jun Liu,Mark A. Eckert,Bryan T. Harada,Song‐Mei Liu,Zhike Lu,Kang‐Kang Yu,Samantha M. Tienda,Agnieszka Chryplewicz,Allen Zhu,Ying Yang,Jing Huang,Shaomin Chen,Zhuo Xu,Xiaohua Leng,Xuechen Yu,Jie Cao,Zezhou Zhang,Jianzhao Liu,Ernst Lengyel,Chuan He
标识
DOI:10.1038/s41556-018-0174-4
摘要
N6-methyladenosine (m6A) messenger RNA methylation is a gene regulatory mechanism affecting cell differentiation and proliferation in development and cancer. To study the roles of m6A mRNA methylation in cell proliferation and tumorigenicity, we investigated human endometrial cancer in which a hotspot R298P mutation is present in a key component of the methyltransferase complex (METTL14). We found that about 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3, another component of the methyltransferase complex. These changes lead to increased proliferation and tumorigenicity of endometrial cancer cells, likely through activation of the AKT pathway. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator mTORC2. Together, these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling. Liu et al. show that reduced m6A mRNA methylation in endometrial cancer is oncogenic. Mechanistically, the AKT pathway is activated in these tumours due to altered expression of AKT regulators carrying m6A on their transcripts.
科研通智能强力驱动
Strongly Powered by AbleSci AI