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Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line

While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression of apoptosis, the mouse NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human NANOS1 p.[(Pro34Thr);(Ser83del)] mutation associated with the absence of...

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Autores principales: Janecki, Damian M., Ilaslan, Erkut, Smialek, Maciej J., Sajek, Marcin P., Kotecki, Maciej, Ginter-Matuszewska, Barbara, Krainski, Patryk, Jaruzelska, Jadwiga, Kusz-Zamelczyk, Kamila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215683/
https://www.ncbi.nlm.nih.gov/pubmed/32344590
http://dx.doi.org/10.3390/ijms21083009
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author Janecki, Damian M.
Ilaslan, Erkut
Smialek, Maciej J.
Sajek, Marcin P.
Kotecki, Maciej
Ginter-Matuszewska, Barbara
Krainski, Patryk
Jaruzelska, Jadwiga
Kusz-Zamelczyk, Kamila
author_facet Janecki, Damian M.
Ilaslan, Erkut
Smialek, Maciej J.
Sajek, Marcin P.
Kotecki, Maciej
Ginter-Matuszewska, Barbara
Krainski, Patryk
Jaruzelska, Jadwiga
Kusz-Zamelczyk, Kamila
author_sort Janecki, Damian M.
collection PubMed
description While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression of apoptosis, the mouse NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human NANOS1 p.[(Pro34Thr);(Ser83del)] mutation associated with the absence of germ cells in seminiferous tubules of infertile patients, which might suggest an anti-apoptotic role of human NANOS1. In this study, we aimed to determine a potential influence of human NANOS1 on the maintenance of TCam-2 model germ cells by investigating proliferation, cell cycle, and apoptosis. Constructs encoding wild-type or mutated human NANOS1 were used for transfection of TCam-2 cells, in order to investigate the effect of NANOS1 on cell proliferation, which was studied using a colorimetric assay, as well as apoptosis and the cell cycle, which were measured by flow cytometry. RNA-Seq (RNA sequencing) analysis followed by RT-qPCR (reverse transcription and quantitative polymerase chain reaction) was conducted for identifying pro-apoptotic genes repressed by NANOS1. Here, we show that overexpression of NANOS1 downregulates apoptosis in TCam-2 cells. Moreover, we found that NANOS1 represses a set of pro-apoptotic genes at the mRNA level. We also found that the infertility-associated p.[(Pro34Thr);(Ser83del)] mutation causes NANOS1 to functionally switch from being anti-apoptotic to pro-apoptotic in the human male germ cell line. Thus, this report is the first to show an anti-apoptotic role of NANOS1 exerted by negative regulation of mRNAs of pro-apoptotic genes.
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spelling pubmed-72156832020-05-22 Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line Janecki, Damian M. Ilaslan, Erkut Smialek, Maciej J. Sajek, Marcin P. Kotecki, Maciej Ginter-Matuszewska, Barbara Krainski, Patryk Jaruzelska, Jadwiga Kusz-Zamelczyk, Kamila Int J Mol Sci Communication While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression of apoptosis, the mouse NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human NANOS1 p.[(Pro34Thr);(Ser83del)] mutation associated with the absence of germ cells in seminiferous tubules of infertile patients, which might suggest an anti-apoptotic role of human NANOS1. In this study, we aimed to determine a potential influence of human NANOS1 on the maintenance of TCam-2 model germ cells by investigating proliferation, cell cycle, and apoptosis. Constructs encoding wild-type or mutated human NANOS1 were used for transfection of TCam-2 cells, in order to investigate the effect of NANOS1 on cell proliferation, which was studied using a colorimetric assay, as well as apoptosis and the cell cycle, which were measured by flow cytometry. RNA-Seq (RNA sequencing) analysis followed by RT-qPCR (reverse transcription and quantitative polymerase chain reaction) was conducted for identifying pro-apoptotic genes repressed by NANOS1. Here, we show that overexpression of NANOS1 downregulates apoptosis in TCam-2 cells. Moreover, we found that NANOS1 represses a set of pro-apoptotic genes at the mRNA level. We also found that the infertility-associated p.[(Pro34Thr);(Ser83del)] mutation causes NANOS1 to functionally switch from being anti-apoptotic to pro-apoptotic in the human male germ cell line. Thus, this report is the first to show an anti-apoptotic role of NANOS1 exerted by negative regulation of mRNAs of pro-apoptotic genes. MDPI 2020-04-24 /pmc/articles/PMC7215683/ /pubmed/32344590 http://dx.doi.org/10.3390/ijms21083009 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Janecki, Damian M.
Ilaslan, Erkut
Smialek, Maciej J.
Sajek, Marcin P.
Kotecki, Maciej
Ginter-Matuszewska, Barbara
Krainski, Patryk
Jaruzelska, Jadwiga
Kusz-Zamelczyk, Kamila
Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title_full Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title_fullStr Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title_full_unstemmed Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title_short Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line
title_sort human nanos1 represses apoptosis by downregulating pro-apoptotic genes in the male germ cell line
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215683/
https://www.ncbi.nlm.nih.gov/pubmed/32344590
http://dx.doi.org/10.3390/ijms21083009
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