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Down-regulation of GADD45A enhances chemosensitivity in melanoma

Melanoma is a malignant skin cancer with considerable drug resistance. Increased expression of DNA repair genes have been reported in melanoma, and this contributes to chemotherapy resistance. GADD45A is involved in DNA repair, cell cycle arrest and apoptosis in response to physiologic or environmen...

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Autores principales: Liu, Jia, Jiang, Guoqiang, Mao, Ping, Zhang, Jing, Zhang, Lin, Liu, Likun, Wang, Jia, Owusu, Lawrence, Ren, Baoyin, Tang, Yawei, Li, Weiling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841426/
https://www.ncbi.nlm.nih.gov/pubmed/29515153
http://dx.doi.org/10.1038/s41598-018-22484-6
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author Liu, Jia
Jiang, Guoqiang
Mao, Ping
Zhang, Jing
Zhang, Lin
Liu, Likun
Wang, Jia
Owusu, Lawrence
Ren, Baoyin
Tang, Yawei
Li, Weiling
author_facet Liu, Jia
Jiang, Guoqiang
Mao, Ping
Zhang, Jing
Zhang, Lin
Liu, Likun
Wang, Jia
Owusu, Lawrence
Ren, Baoyin
Tang, Yawei
Li, Weiling
author_sort Liu, Jia
collection PubMed
description Melanoma is a malignant skin cancer with considerable drug resistance. Increased expression of DNA repair genes have been reported in melanoma, and this contributes to chemotherapy resistance. GADD45A is involved in DNA repair, cell cycle arrest and apoptosis in response to physiologic or environmental stresses. In this study, we investigated the role of GADD45A in chemotherapy response. Firstly, the mRNA expression of profiled DNA repair genes in cisplatin-treated melanoma cells was detected by RT(2) profiler(TM) PCR array. We found the expression of GADD45A upregulated in a dose- and time- dependent manner. In addition, suppression of GADD45A sensitized melanoma cells to cisplatin and enhanced cisplatin-induced DNA damage. Flow cytometry revealed that downregulating GADD45A released cells from cisplatin-induced G2/M arrest and increased apoptosis. By using a MEK inhibitor, GADD45A was shown to be regulated by MAPK-ERK pathway following cisplatin treatment. Thus, the induction of GADD45A might play important roles in chemotherapy response in human melanoma cancer and could serve as a novel molecular target for melanoma therapy.
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spelling pubmed-58414262018-03-14 Down-regulation of GADD45A enhances chemosensitivity in melanoma Liu, Jia Jiang, Guoqiang Mao, Ping Zhang, Jing Zhang, Lin Liu, Likun Wang, Jia Owusu, Lawrence Ren, Baoyin Tang, Yawei Li, Weiling Sci Rep Article Melanoma is a malignant skin cancer with considerable drug resistance. Increased expression of DNA repair genes have been reported in melanoma, and this contributes to chemotherapy resistance. GADD45A is involved in DNA repair, cell cycle arrest and apoptosis in response to physiologic or environmental stresses. In this study, we investigated the role of GADD45A in chemotherapy response. Firstly, the mRNA expression of profiled DNA repair genes in cisplatin-treated melanoma cells was detected by RT(2) profiler(TM) PCR array. We found the expression of GADD45A upregulated in a dose- and time- dependent manner. In addition, suppression of GADD45A sensitized melanoma cells to cisplatin and enhanced cisplatin-induced DNA damage. Flow cytometry revealed that downregulating GADD45A released cells from cisplatin-induced G2/M arrest and increased apoptosis. By using a MEK inhibitor, GADD45A was shown to be regulated by MAPK-ERK pathway following cisplatin treatment. Thus, the induction of GADD45A might play important roles in chemotherapy response in human melanoma cancer and could serve as a novel molecular target for melanoma therapy. Nature Publishing Group UK 2018-03-07 /pmc/articles/PMC5841426/ /pubmed/29515153 http://dx.doi.org/10.1038/s41598-018-22484-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Jia
Jiang, Guoqiang
Mao, Ping
Zhang, Jing
Zhang, Lin
Liu, Likun
Wang, Jia
Owusu, Lawrence
Ren, Baoyin
Tang, Yawei
Li, Weiling
Down-regulation of GADD45A enhances chemosensitivity in melanoma
title Down-regulation of GADD45A enhances chemosensitivity in melanoma
title_full Down-regulation of GADD45A enhances chemosensitivity in melanoma
title_fullStr Down-regulation of GADD45A enhances chemosensitivity in melanoma
title_full_unstemmed Down-regulation of GADD45A enhances chemosensitivity in melanoma
title_short Down-regulation of GADD45A enhances chemosensitivity in melanoma
title_sort down-regulation of gadd45a enhances chemosensitivity in melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841426/
https://www.ncbi.nlm.nih.gov/pubmed/29515153
http://dx.doi.org/10.1038/s41598-018-22484-6
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