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

Cancers
Adriana AmaroRosaria Gangemi

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...Continue Reading

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Citations

Aug 13, 2020·International Journal of Molecular Sciences·Karen AughtonSarah E Coupland
Aug 13, 2020·Cellular and Molecular Life Sciences : CMLS·Chun YangPierre Hardy
May 11, 2021·Frontiers in Oncology·Soudeh Ghafouri-FardMohammad Taheri
Aug 27, 2021·Acta Biochimica Et Biophysica Sinica·Ming LiYubo Xiao

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Methods Mentioned

BETA
Transfection
xenograft
Assay
PCR
FCS
enzyme-linked immunosorbent assay

Software Mentioned

CellQuest
Graph
PRISM
Miranda
Xena
Xenabrowser
- Pad

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