RNA m6A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c‐Met. Issue 10 (4th February 2020)

• Record Type: Journal Article
• Authors: Luo, Guangying; Xu, Weiwei; Zhao, Yunping; Jin, Shanshan; Wang, Siqi; Liu, Qi; Chen, Xiaoyan; Wang, Jiao; Dong, Feng; Hu, Dan‐Ning; Reinach, Peter S.; Yan, Dongsheng
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 10(2020:Oct.)
• Page Start: 7107
• Page End: 7119
• Publication Date: 2020-02-04
• Subjects: c‐Met -- migration -- proliferation -- RNA m6A methylation -- uveal melanoma; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29608
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : METTL3‐mediated m 6 A RNA methylation promotes uveal melanoma cell proliferation, migration, and invasion by targeting c‐Met. Such modification acts as a critical oncogenic regulator in uveal melanoma development.