| Literature DB >> 30154548 |
Jun Liu1,2, Mark A Eckert3, Bryan T Harada1,2, Song-Mei Liu4, Zhike Lu1,2, Kangkang Yu1,2,5, Samantha M Tienda3, Agnieszka Chryplewicz3, Allen C Zhu1,2,6, Ying Yang4, Jing-Tao Huang4, Shao-Min Chen4, Zhi-Gao Xu7, Xiao-Hua Leng8, Xue-Chen Yu9, Jie Cao10, Zezhou Zhang10, Jianzhao Liu10, Ernst Lengyel11, Chuan He12,13,14.
Abstract
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.Entities:
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Year: 2018 PMID： 30154548 PMCID： PMC6245953 DOI： 10.1038/s41556-018-0174-4
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824