Abstract
Purpose :
GNAQ is a heterotrimeric G protein alpha subunit, which when mutated can act as an oncogene. Such a change can make it a crucial contributor to the development of uveal melanoma. There are numerous studies showing that aberrant microRNA (miRNA) expression patterns contribute to tumorigenesis. However, whether GNAQ can be modulated by miRNA, remains elusive. In a previous study, we reported that miR-1 can inhibit uveal melanoma cell proliferation and migration through the c-Met pathway. Here, we determined whether miR-1 regulates GNAQ expression in uveal melanoma cells.
Methods :
Bioinformatics predicted miR-1 gene targets. Luciferase reporter assay validated putative target identity. MiR-1 or GNAQ specific siRNA was transfected into uveal melanoma cells by Lipofectamine RNAiMAX reagent. Western blot analysis was carried out to detect GNAQ expression in uveal melanoma cells. Cell proliferation and migration were measured by MTS and transwell assay, respectively.
Results :
GNAQ was identified as a bona fide target of miR-1. Ectopic miR-1 downregulated GNAQ expression in uveal melanoma cells. Downregulation of GNAQ significantly inhibited uveal melanoma cell proliferation and migration.
Conclusions :
Our results demonstrated that GNAQ is a miR-1 gene target in uveal melanoma cells. MiR-1 may be a promising drug target to treat uveal melanoma due to its pleiotropic regulation of multiple oncogenes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.