Journal of cellular physiologyFeb 5, 2020

RNA m6A methylation may control uveal melanoma cell growth and movement by affecting c-Met

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

Global RNA mA methylation levels were dramatically elevated in both uveal melanoma (UM) cell lines and clinical specimens.

METTL3, a key enzyme regulating mA methylation, was significantly increased in UM cells and specimens.
Blocking mA methylation through either cycloleucine or silencing METTL3 suppressed UM cell proliferation and colony formation.
Inhibition of METTL3 led to cell cycle G1 arrest and reduced migration and invasion of UM cells.
Overexpression of METTL3 had the opposite effects, promoting UM cell proliferation and invasion.
c-Met was identified as a direct target of mA methylation in UM cells, with its expression downregulated by inhibiting METTL3.

Simplified

N-methyladenosine (mA) is a novel epitranscriptomic marker that contributes to regulating diverse biological processes through controlling messenger RNA metabolism. However, it is unknown if mA 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 mA methylation levels were dramatically elevated in both UM cell lines and clinical specimens. Meanwhile, we found that METTL3, a main mA regulatory enzyme, was significantly increased in UM cells and specimens. Subsequently, cycloleucine (Cyc) or METTL3 targeted small interfering RNA was used to block mA 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 mA 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 mA 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. 6 6 6 6 6 6 6 6

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RNA m6A methylation may control uveal melanoma cell growth and movement by affecting c-Met

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