Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition
Open Access
- 4 June 2020
- Vol. 12 (6), 1468
- https://doi.org/10.3390/cancers12061468
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 ADAM10 and c-Met 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 ADAM10 and c-Met. 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.Funding Information
- Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 17103).)
- Compagnia di San Paolo (Prot. : 2017.AAI4504.U5092)
This publication has 55 references indexed in Scilit:
- Role of MicroRNA-182 in Posterior Uveal Melanoma: Regulation of Tumor Development through MITF, BCL2 and Cyclin D2PLOS ONE, 2012
- Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated NanoparticlesPLOS ONE, 2012
- Mda-9/Syntenin Is Expressed in Uveal Melanoma and Correlates with Metastatic ProgressionPLOS ONE, 2012
- Frequent Mutation of BAP1 in Metastasizing Uveal MelanomasScience, 2010
- Mutations inGNA11in Uveal MelanomaThe New England Journal of Medicine, 2010
- MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to SorafenibOnline Journal of Public Health Informatics, 2009
- MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinomaHepatology, 2008
- Frequent somatic mutations of GNAQ in uveal melanoma and blue naeviNature, 2008
- Melanomas that develop within the eye inhibit lymphocyte proliferationInternational Journal of Cancer, 1997
- Establishment and characterization of an uveal‐melanoma cell lineInternational Journal of Cancer, 1995