Potential Onco-Suppressive Role of MiR122 and MiR144 in Uveal Melanoma Through ADAM10 and C-Met Inhibition

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Jun 10

PMID 32512881

Citations 9

Authors

Adriana Amaro

Michela Croce

Silvano Ferrini

Gaia Barisione

Marina Gualco

Patrizia Perri

Ulrich Pfeffer

Martine J Jager

Sarah E Coupland

Carlo Mosci

Gilberto Filaci

Marina Fabbi

Paola Queirolo

Rosaria Gangemi

Affiliations

Soon will be listed here.

Abstract

Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate and expression in different settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression by miR microarray, RT-qPCR, Western blotting, miR transfection and luciferase reporter assay. Our results indicate that miR122 and miR144 are expressed at low levels in the UM cell lines and in the TCGA UM dataset and were down-modulated in a cohort of seven UM samples, compared to normal choroid. Both miR122 and miR144 directly targeted and . Overexpression of miR122 and miR144 led to reduced expression of ADAM10 and c-Met in the UM cell lines and impaired cell proliferation, migration, cell cycle and shedding of c-Met ecto-domain. Our results show that miR122 and miR144 display an onco-suppressive role in UM through ADAM10 and c-Met modulation.

Citing Articles

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