Premium
RNA m 6 A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c‐Met
Author(s) -
Luo Guangying,
Xu Weiwei,
Zhao Yunping,
Jin Shanshan,
Wang Siqi,
Liu Qi,
Chen Xiaoyan,
Wang Jiao,
Dong Feng,
Hu DanNing,
Reinach Peter S.,
Yan Dongsheng
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29608
Subject(s) - methylation , rna methylation , cell growth , rna , gene knockdown , small interfering rna , gene silencing , biology , microbiology and biotechnology , cell cycle , cell , cancer research , messenger rna , immunoprecipitation , methyltransferase , cell culture , biochemistry , gene , genetics
N 6 ‐methyladenosine (m 6 A) is a novel epitranscriptomic marker that contributes to regulating diverse biological processes through controlling messenger RNA metabolism. However, it is unknown if m 6 A RNA methylation affects uveal melanoma (UM) development. To address this question, we probed its function and molecular mechanism in UM. Initially, we demonstrated that global RNA m 6 A methylation levels were dramatically elevated in both UM cell lines and clinical specimens. Meanwhile, we found that METTL3, a main m 6 A regulatory enzyme, was significantly increased in UM cells and specimens. Subsequently, cycloleucine (Cyc) or METTL3 targeted small interfering RNA was used to block m 6 A methylation in UM cells. We found that Cyc or silencing METTL3 significantly suppressed UM cell proliferation and colony formation through cell cycle G1 arrest, as well as migration and invasion by functional analysis. On the other hand, overexpression of METTL3 had the opposite effects. Furthermore, bioinformatics and methylated RNA immunoprecipitation‐quantitative polymerase chain reaction identified c‐Met as a direct target of m 6 A methylation in UM cells. In addition, western blot analysis showed that Cyc or knockdown of METTL3 downregulated c‐Met, p‐Akt, and cell cycle‐related protein levels in UM cells. Taken together, our results demonstrate that METTL3‐mediated m 6 A RNA methylation modulates UM cell proliferation, migration, and invasion by targeting c‐Met. Such a modification acts as a critical oncogenic regulator in UM development.