Regulation of cancer aggressive features in melanoma cells by microRNAs.
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here...
Guardado en:
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2011
|
Materias: | |
Acceso en línea: | https://doaj.org/article/c83c8eb018fb4a90a218b7a8494a17e4 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:c83c8eb018fb4a90a218b7a8494a17e4 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:c83c8eb018fb4a90a218b7a8494a17e42021-11-18T06:55:14ZRegulation of cancer aggressive features in melanoma cells by microRNAs.1932-620310.1371/journal.pone.0018936https://doaj.org/article/c83c8eb018fb4a90a218b7a8494a17e42011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21541354/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells. To avoid differences due to genetic background, a comparative high-throughput miRNA profiling was performed on two isogenic human melanoma cell lines that display major differences in their net proliferation, invasion and tube formation activities. This screening revealed two major cohorts of differentially expressed miRNAs. We speculated that miRNAs up-regulated in the more-aggressive cell line contribute oncogenic features, while the down-regulated miRNAs are tumor suppressive. This assumption was further tested experimentally on five candidate tumor suppressive miRNAs (miR-31, -34a, -184, -185 and -204) and on one candidate oncogenic miRNA (miR-17-5p), all of which have never been reported before in cutaneous melanoma. Remarkably, all candidate Suppressive-miRNAs inhibited net proliferation, invasion or tube formation, while miR-17-5p enhanced cell proliferation. miR-34a and miR-185 were further shown to inhibit the growth of melanoma xenografts when implanted in SCID-NOD mice. Finally, all six candidate miRNAs were detected in 15 different metastatic melanoma specimens, attesting for the physiological relevance of our findings. Collectively, these findings may prove instrumental for understanding mechanisms of disease and for development of novel therapeutic and staging technologies for melanoma.Eyal GreenbergLiat HershkovitzOrit ItzhakiSteven HajduYael NemlichRona OrtenbergNir GefenLiat EdryShira ModaiYona KeisariMichal J BesserJacob SchachterNoam ShomronGal MarkelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18936 (2011) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Eyal Greenberg Liat Hershkovitz Orit Itzhaki Steven Hajdu Yael Nemlich Rona Ortenberg Nir Gefen Liat Edry Shira Modai Yona Keisari Michal J Besser Jacob Schachter Noam Shomron Gal Markel Regulation of cancer aggressive features in melanoma cells by microRNAs. |
description |
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells. To avoid differences due to genetic background, a comparative high-throughput miRNA profiling was performed on two isogenic human melanoma cell lines that display major differences in their net proliferation, invasion and tube formation activities. This screening revealed two major cohorts of differentially expressed miRNAs. We speculated that miRNAs up-regulated in the more-aggressive cell line contribute oncogenic features, while the down-regulated miRNAs are tumor suppressive. This assumption was further tested experimentally on five candidate tumor suppressive miRNAs (miR-31, -34a, -184, -185 and -204) and on one candidate oncogenic miRNA (miR-17-5p), all of which have never been reported before in cutaneous melanoma. Remarkably, all candidate Suppressive-miRNAs inhibited net proliferation, invasion or tube formation, while miR-17-5p enhanced cell proliferation. miR-34a and miR-185 were further shown to inhibit the growth of melanoma xenografts when implanted in SCID-NOD mice. Finally, all six candidate miRNAs were detected in 15 different metastatic melanoma specimens, attesting for the physiological relevance of our findings. Collectively, these findings may prove instrumental for understanding mechanisms of disease and for development of novel therapeutic and staging technologies for melanoma. |
format |
article |
author |
Eyal Greenberg Liat Hershkovitz Orit Itzhaki Steven Hajdu Yael Nemlich Rona Ortenberg Nir Gefen Liat Edry Shira Modai Yona Keisari Michal J Besser Jacob Schachter Noam Shomron Gal Markel |
author_facet |
Eyal Greenberg Liat Hershkovitz Orit Itzhaki Steven Hajdu Yael Nemlich Rona Ortenberg Nir Gefen Liat Edry Shira Modai Yona Keisari Michal J Besser Jacob Schachter Noam Shomron Gal Markel |
author_sort |
Eyal Greenberg |
title |
Regulation of cancer aggressive features in melanoma cells by microRNAs. |
title_short |
Regulation of cancer aggressive features in melanoma cells by microRNAs. |
title_full |
Regulation of cancer aggressive features in melanoma cells by microRNAs. |
title_fullStr |
Regulation of cancer aggressive features in melanoma cells by microRNAs. |
title_full_unstemmed |
Regulation of cancer aggressive features in melanoma cells by microRNAs. |
title_sort |
regulation of cancer aggressive features in melanoma cells by micrornas. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/c83c8eb018fb4a90a218b7a8494a17e4 |
work_keys_str_mv |
AT eyalgreenberg regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT liathershkovitz regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT orititzhaki regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT stevenhajdu regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT yaelnemlich regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT ronaortenberg regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT nirgefen regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT liatedry regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT shiramodai regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT yonakeisari regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT michaljbesser regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT jacobschachter regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT noamshomron regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas AT galmarkel regulationofcanceraggressivefeaturesinmelanomacellsbymicrornas |
_version_ |
1718424193520893952 |