RNA m⁶A Methylation Regulates Uveal Melanoma Cell Proliferation and Migration by Targeting c-Met

Abstract

Purpose : N⁶-methyladenosine (m⁶A) is a universal mRNA modification which can regulate gene expression through control of mRNA translation and degradation. Emerging evidence indicates that such modification contributes to regulating diverse biological processes. However, it is unclear whether RNA m⁶A methylation affects uveal melanoma development. In this study, we investigated the role of m⁶A methylation in regulating uveal melanoma cell proliferation and migration.

Methods : Dot blot determined m⁶A methylation levels in uveal melanoma cells and uveal melanocytes. M⁶A methylation inhibitor-cycloleucine, was used to evaluate the effects of m⁶A methylation on uveal melanoma cell proliferation and migration. These responses were measured by MTS and transwell assay, respectively. Western blot analysis was carried out to detect c-Met expression levels in uveal melanoma cells.

Results : RNA m⁶A methylation level was dramatically upregulated in uveal melanoma cells as compared with uveal melanocytes. M⁶A inhibitor significantly suppressed uveal melanoma cell proliferation and migration. Furthermore, inhibition of m⁶A methylation downregulated c-Met expression in uveal melanoma cells.

Conclusions : Our results demonstrate that RNA m⁶A methylation can modulate uveal melanoma cell proliferation and migration through targeting c-Met. Targeting m⁶A methylation may be a promising avenue to treat uveal melanoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.