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Loss of miR-1469 expression mediates melanoma cell migration and invasion

Tumor ulceration is considered one of the most prognostically significant findings in primary cutaneous melanoma, associated with decreased disease-free and overall survival. However, the unique features associated with ulcerated melanoma that contribute to a poor prognosis in affected patients rema...

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Autores principales: DiVincenzo, Mallory J., Barricklow, Zoe, Schwarz, Emily, Moufawad, Maribelle, Howard, J. Harrison, Yu, Lianbo, Chung, Catherine, Gru, Alejandro A., Carson, William E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409617/
https://www.ncbi.nlm.nih.gov/pubmed/34469478
http://dx.doi.org/10.1371/journal.pone.0256629
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author DiVincenzo, Mallory J.
Barricklow, Zoe
Schwarz, Emily
Moufawad, Maribelle
Howard, J. Harrison
Yu, Lianbo
Chung, Catherine
Gru, Alejandro A.
Carson, William E.
author_facet DiVincenzo, Mallory J.
Barricklow, Zoe
Schwarz, Emily
Moufawad, Maribelle
Howard, J. Harrison
Yu, Lianbo
Chung, Catherine
Gru, Alejandro A.
Carson, William E.
author_sort DiVincenzo, Mallory J.
collection PubMed
description Tumor ulceration is considered one of the most prognostically significant findings in primary cutaneous melanoma, associated with decreased disease-free and overall survival. However, the unique features associated with ulcerated melanoma that contribute to a poor prognosis in affected patients remain poorly defined. microRNAs are small, non-coding RNAs that function to inhibit expression of specific gene targets, therefore altering the functions of cells in which they are expressed. miR-1469 is a novel miR with significantly decreased expression in ulcerated melanoma tissue relative to non-ulcerated tumors. We hypothesized that loss of miR-1469 expression in melanoma contributes to altered tumor cell functions mediating disease progression. Transfection of a miR-1469 mimic resulted in a significant reduction in the migratory and invasive capacity of the CHL1 and MEL39 melanoma cell lines (>58.1% reduction, p < 0.0332), as well as the invasive capacity of the A375 melanoma cell line (>50% reduction, p < 0.0021). Expression of myeloid cell leukemia-1 (MCL1), a miR-1469 target gene, was reduced in the A375 and MEL39 cell lines by immunoblot. No significant differences in viability, resistance to apoptotic stimuli, or proliferation were observed following transfection. These findings together demonstrate how migration and invasion are specific functions through which miR-1469 expression in melanoma cells can contribute to the differences in disease progression associated with tumor ulceration.
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spelling pubmed-84096172021-09-02 Loss of miR-1469 expression mediates melanoma cell migration and invasion DiVincenzo, Mallory J. Barricklow, Zoe Schwarz, Emily Moufawad, Maribelle Howard, J. Harrison Yu, Lianbo Chung, Catherine Gru, Alejandro A. Carson, William E. PLoS One Research Article Tumor ulceration is considered one of the most prognostically significant findings in primary cutaneous melanoma, associated with decreased disease-free and overall survival. However, the unique features associated with ulcerated melanoma that contribute to a poor prognosis in affected patients remain poorly defined. microRNAs are small, non-coding RNAs that function to inhibit expression of specific gene targets, therefore altering the functions of cells in which they are expressed. miR-1469 is a novel miR with significantly decreased expression in ulcerated melanoma tissue relative to non-ulcerated tumors. We hypothesized that loss of miR-1469 expression in melanoma contributes to altered tumor cell functions mediating disease progression. Transfection of a miR-1469 mimic resulted in a significant reduction in the migratory and invasive capacity of the CHL1 and MEL39 melanoma cell lines (>58.1% reduction, p < 0.0332), as well as the invasive capacity of the A375 melanoma cell line (>50% reduction, p < 0.0021). Expression of myeloid cell leukemia-1 (MCL1), a miR-1469 target gene, was reduced in the A375 and MEL39 cell lines by immunoblot. No significant differences in viability, resistance to apoptotic stimuli, or proliferation were observed following transfection. These findings together demonstrate how migration and invasion are specific functions through which miR-1469 expression in melanoma cells can contribute to the differences in disease progression associated with tumor ulceration. Public Library of Science 2021-09-01 /pmc/articles/PMC8409617/ /pubmed/34469478 http://dx.doi.org/10.1371/journal.pone.0256629 Text en © 2021 DiVincenzo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
DiVincenzo, Mallory J.
Barricklow, Zoe
Schwarz, Emily
Moufawad, Maribelle
Howard, J. Harrison
Yu, Lianbo
Chung, Catherine
Gru, Alejandro A.
Carson, William E.
Loss of miR-1469 expression mediates melanoma cell migration and invasion
title Loss of miR-1469 expression mediates melanoma cell migration and invasion
title_full Loss of miR-1469 expression mediates melanoma cell migration and invasion
title_fullStr Loss of miR-1469 expression mediates melanoma cell migration and invasion
title_full_unstemmed Loss of miR-1469 expression mediates melanoma cell migration and invasion
title_short Loss of miR-1469 expression mediates melanoma cell migration and invasion
title_sort loss of mir-1469 expression mediates melanoma cell migration and invasion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409617/
https://www.ncbi.nlm.nih.gov/pubmed/34469478
http://dx.doi.org/10.1371/journal.pone.0256629
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