Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells

Melanoma is highly heterogeneous type of malignant neoplasm that is responsible for the majority of deaths among other types of skin cancer. In the present study, we screened a list of differentially expressed genes in two primary, drug-naïve melanoma cell lines derived from patients with melanoma f...

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Autores principales:	Anna Tyumentseva, Anton Averchuk, Nadezhda Palkina, Ivan Zinchenko, Anton Moshev, Andrey Savchenko, Tatiana Ruksha
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	migration transcriptome dacarbazine PLNXA2 melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c35535fb6841488d94f6b239aa803d49
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spelling	oai:doaj.org-article:c35535fb6841488d94f6b239aa803d492021-12-03T04:39:33ZTranscriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells2234-943X10.3389/fonc.2021.732501https://doaj.org/article/c35535fb6841488d94f6b239aa803d492021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.732501/fullhttps://doaj.org/toc/2234-943XMelanoma is highly heterogeneous type of malignant neoplasm that is responsible for the majority of deaths among other types of skin cancer. In the present study, we screened a list of differentially expressed genes in two primary, drug-naïve melanoma cell lines derived from patients with melanoma following treatment of the cells with the chemotherapeutic agent dacarbazine. The aim was to determine the transcriptomic profiles and associated alterations in the cell phenotype. We found the vascular endothelial growth factor A/vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase/protein kinase B and focal adhesion signaling pathways to be top altered after dacarbazine treatment. In addition, we observed the expression levels of genes associated with tumor dissemination, integrin β8 and matrix metalloproteinase-1, to be diminished in both cell lines studied, the results of which were confirmed by reverse transcription-quantitative polymerase chain reaction. By contrast, plexin A2 expression was found to be upregulated in K2303 cells, where reduced migration and invasion were also observed, following dacarbazine treatment. Plexin A2 downregulation was associated with the promotion of migrative and invasive capacities in B0404 melanoma cells. Since plexin A2 is semaphorin co-receptor that is involved in focal adhesion and cell migration regulation, the present study suggested that plexin A2 may be implicated in the dacarbazine-mediated phenotypic shift of melanoma cells. We propose that the signature of cancer cell invasiveness can be revealed by using a combination of transcriptomic and functional approaches, which should be applied in the development of personalized therapeutic strategies for each patient with melanoma.Anna TyumentsevaAnna TyumentsevaAnton AverchukNadezhda PalkinaIvan ZinchenkoAnton MoshevAndrey SavchenkoTatiana RukshaFrontiers Media S.A.articlemigrationtranscriptomedacarbazinePLNXA2melanomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	migration transcriptome dacarbazine PLNXA2 melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	migration transcriptome dacarbazine PLNXA2 melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Anna Tyumentseva Anna Tyumentseva Anton Averchuk Nadezhda Palkina Ivan Zinchenko Anton Moshev Andrey Savchenko Tatiana Ruksha Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
description	Melanoma is highly heterogeneous type of malignant neoplasm that is responsible for the majority of deaths among other types of skin cancer. In the present study, we screened a list of differentially expressed genes in two primary, drug-naïve melanoma cell lines derived from patients with melanoma following treatment of the cells with the chemotherapeutic agent dacarbazine. The aim was to determine the transcriptomic profiles and associated alterations in the cell phenotype. We found the vascular endothelial growth factor A/vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase/protein kinase B and focal adhesion signaling pathways to be top altered after dacarbazine treatment. In addition, we observed the expression levels of genes associated with tumor dissemination, integrin β8 and matrix metalloproteinase-1, to be diminished in both cell lines studied, the results of which were confirmed by reverse transcription-quantitative polymerase chain reaction. By contrast, plexin A2 expression was found to be upregulated in K2303 cells, where reduced migration and invasion were also observed, following dacarbazine treatment. Plexin A2 downregulation was associated with the promotion of migrative and invasive capacities in B0404 melanoma cells. Since plexin A2 is semaphorin co-receptor that is involved in focal adhesion and cell migration regulation, the present study suggested that plexin A2 may be implicated in the dacarbazine-mediated phenotypic shift of melanoma cells. We propose that the signature of cancer cell invasiveness can be revealed by using a combination of transcriptomic and functional approaches, which should be applied in the development of personalized therapeutic strategies for each patient with melanoma.
format	article
author	Anna Tyumentseva Anna Tyumentseva Anton Averchuk Nadezhda Palkina Ivan Zinchenko Anton Moshev Andrey Savchenko Tatiana Ruksha
author_facet	Anna Tyumentseva Anna Tyumentseva Anton Averchuk Nadezhda Palkina Ivan Zinchenko Anton Moshev Andrey Savchenko Tatiana Ruksha
author_sort	Anna Tyumentseva
title	Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
title_short	Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
title_full	Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
title_fullStr	Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
title_full_unstemmed	Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells
title_sort	transcriptomic profiling revealed plexin a2 downregulation with migration and invasion alteration in dacarbazine-treated primary melanoma cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c35535fb6841488d94f6b239aa803d49
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Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells

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