Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. He...

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Main Authors:	Monica Currò, Nadia Ferlazzo, Maria Laura Giunta, Angela Simona Montalto, Tiziana Russo, Salvatore Arena, Pietro Impellizzeri, Daniela Caccamo, Carmelo Romeo, Riccardo Ientile
Format:	Article
Language:	English
Published:	MDPI AG 2020-02-01
Series:	International Journal of Molecular Sciences
Subjects:	hif-1α hypoxia mycn neuroblastoma transglutaminase isoforms
Online Access:	https://www.mdpi.com/1422-0067/21/4/1364

id	doaj-39346b462f6645508ca8908c12875742
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spelling	doaj-39346b462f6645508ca8908c128757422020-11-25T02:03:34ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01214136410.3390/ijms21041364ijms21041364Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification StatusMonica Currò0Nadia Ferlazzo1Maria Laura Giunta2Angela Simona Montalto3Tiziana Russo4Salvatore Arena5Pietro Impellizzeri6Daniela Caccamo7Carmelo Romeo8Riccardo Ientile9Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi,” University of Messina, 98125 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi,” University of Messina, 98125 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi,” University of Messina, 98125 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi,” University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyDepartment of Human Pathology of Adult and Childhood “Gaetano Barresi,” University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyTransglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, <i>p16</i>, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-<i>MYCN</i>-amplified) and IMR-32 (<i>MYCN</i>-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of <i>HIF-1α</i> in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of <i>MYCN</i> amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.https://www.mdpi.com/1422-0067/21/4/1364hif-1αhypoxiamycnneuroblastomatransglutaminase isoforms
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Monica Currò Nadia Ferlazzo Maria Laura Giunta Angela Simona Montalto Tiziana Russo Salvatore Arena Pietro Impellizzeri Daniela Caccamo Carmelo Romeo Riccardo Ientile
spellingShingle	Monica Currò Nadia Ferlazzo Maria Laura Giunta Angela Simona Montalto Tiziana Russo Salvatore Arena Pietro Impellizzeri Daniela Caccamo Carmelo Romeo Riccardo Ientile Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status International Journal of Molecular Sciences hif-1α hypoxia mycn neuroblastoma transglutaminase isoforms
author_facet	Monica Currò Nadia Ferlazzo Maria Laura Giunta Angela Simona Montalto Tiziana Russo Salvatore Arena Pietro Impellizzeri Daniela Caccamo Carmelo Romeo Riccardo Ientile
author_sort	Monica Currò
title	Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
title_short	Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
title_full	Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
title_fullStr	Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
title_full_unstemmed	Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status
title_sort	hypoxia-dependent expression of tg2 isoforms in neuroblastoma cells as consequence of different mycn amplification status
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1422-0067
publishDate	2020-02-01
description	Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, <i>p16</i>, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-<i>MYCN</i>-amplified) and IMR-32 (<i>MYCN</i>-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of <i>HIF-1α</i> in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of <i>MYCN</i> amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.
topic	hif-1α hypoxia mycn neuroblastoma transglutaminase isoforms
url	https://www.mdpi.com/1422-0067/21/4/1364
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Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

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