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Article

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

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IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
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Azienda Sociosanitaria Ligure 3 (ASL3), Sistema Sanitario Regionale Liguria, 16149 Genova, Italy
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Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto G. Gaslini|Ospedale Pediatrico Gaslini, 16147 Genova, Italy
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Leiden University Medical Center, 2333ZA Leiden, The Netherlands
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Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L7 8TX, UK
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Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK
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Galliera Hospital, 16128 Genova, Italy
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Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Via De Toni 14, 16132 Genova, Italy
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IEO Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2020, 12(6), 1468; https://doi.org/10.3390/cancers12061468
Received: 18 May 2020 / Revised: 1 June 2020 / Accepted: 2 June 2020 / Published: 4 June 2020
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. View Full-Text
Keywords: uveal melanoma; miRNA; ADAM10; c-Met; onco-suppressor uveal melanoma; miRNA; ADAM10; c-Met; onco-suppressor
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MDPI and ACS Style

Amaro, A.; Croce, M.; Ferrini, S.; Barisione, G.; Gualco, M.; Perri, P.; Pfeffer, U.; Jager, M.J.; Coupland, S.E.; Mosci, C.; Filaci, G.; Fabbi, M.; Queirolo, P.; Gangemi, R. Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition. Cancers 2020, 12, 1468. https://doi.org/10.3390/cancers12061468

AMA Style

Amaro A, Croce M, Ferrini S, Barisione G, Gualco M, Perri P, Pfeffer U, Jager MJ, Coupland SE, Mosci C, Filaci G, Fabbi M, Queirolo P, Gangemi R. Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition. Cancers. 2020; 12(6):1468. https://doi.org/10.3390/cancers12061468

Chicago/Turabian Style

Amaro, Adriana, 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, and Rosaria Gangemi. 2020. "Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition" Cancers 12, no. 6: 1468. https://doi.org/10.3390/cancers12061468

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