PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes

Abstract Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a c...

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Autores principales:	Takahito Ohira, Suguru Nakagawa, Jumpei Takeshita, Hiroyuki Aburatani, Hiroyuki Kugoh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3176cc63343c4e699dbf435835633c21
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spelling	oai:doaj.org-article:3176cc63343c4e699dbf435835633c212021-12-02T17:25:33ZPITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes10.1038/s41598-021-97791-62045-2322https://doaj.org/article/3176cc63343c4e699dbf435835633c212021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97791-6https://doaj.org/toc/2045-2322Abstract Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (SOX) gene family mRNA transcription. Overexpression of PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the SOX9 promoter region as a positive regulatory transcription factor; PITX1 mRNA expression levels were positively correlated with SOX9 expression, and negatively correlated with SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON), was decreased in PITX1-overexpressing cells. Taken together, the findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling.Takahito OhiraSuguru NakagawaJumpei TakeshitaHiroyuki AburataniHiroyuki KugohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takahito Ohira Suguru Nakagawa Jumpei Takeshita Hiroyuki Aburatani Hiroyuki Kugoh PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
description	Abstract Melanoma is one of the most aggressive types of cancer wherein resistance to treatment prevails. Therefore, it is important to discover novel molecular targets of melanoma progression as potential treatments. Here we show that paired-like homeodomain transcription factor 1 (PITX1) plays a crucial role in the inhibition of melanoma progression through regulation of SRY-box transcription factors (SOX) gene family mRNA transcription. Overexpression of PITX1 in melanoma cell lines resulted in a reduction in cell proliferation and an increase in apoptosis. Additionally, analysis of protein levels revealed an antagonistic cross-regulation between SOX9 and SOX10. Interestingly, PITX1 binds to the SOX9 promoter region as a positive regulatory transcription factor; PITX1 mRNA expression levels were positively correlated with SOX9 expression, and negatively correlated with SOX10 expression in melanoma tissues. Furthermore, transcription of the long noncoding RNA (lncRNA), survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON), was decreased in PITX1-overexpressing cells. Taken together, the findings in this study indicate that PITX1 may act as a negative regulatory factor in the development and progression of melanoma via direct targeting of the SOX signaling.
format	article
author	Takahito Ohira Suguru Nakagawa Jumpei Takeshita Hiroyuki Aburatani Hiroyuki Kugoh
author_facet	Takahito Ohira Suguru Nakagawa Jumpei Takeshita Hiroyuki Aburatani Hiroyuki Kugoh
author_sort	Takahito Ohira
title	PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
title_short	PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
title_full	PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
title_fullStr	PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
title_full_unstemmed	PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes
title_sort	pitx1 inhibits the growth and proliferation of melanoma cells through regulation of sox family genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3176cc63343c4e699dbf435835633c21
work_keys_str_mv	AT takahitoohira pitx1inhibitsthegrowthandproliferationofmelanomacellsthroughregulationofsoxfamilygenes AT sugurunakagawa pitx1inhibitsthegrowthandproliferationofmelanomacellsthroughregulationofsoxfamilygenes AT jumpeitakeshita pitx1inhibitsthegrowthandproliferationofmelanomacellsthroughregulationofsoxfamilygenes AT hiroyukiaburatani pitx1inhibitsthegrowthandproliferationofmelanomacellsthroughregulationofsoxfamilygenes AT hiroyukikugoh pitx1inhibitsthegrowthandproliferationofmelanomacellsthroughregulationofsoxfamilygenes
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PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes

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