NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells

NK2 homeobox 1 (NKX2-1) is a thyroid transcription factor essential for proper thyroid formation and maintaining its physiological function. In thyroid cancer, NKX2-1 expression decreases in parallel with declined differentiation. However, the molecular pathways and mechanisms connecting NKX2-1 to t...

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Autores principales: Yuko Ito, Fumihiko Furuya, Katsumi Taki, Hideaki Suzuki, Hiroki Shimura
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/0c6dd759a1584754b8767fff4bc3d876
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spelling oai:doaj.org-article:0c6dd759a1584754b8767fff4bc3d8762021-11-18T06:34:27ZNKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells1932-6203https://doaj.org/article/0c6dd759a1584754b8767fff4bc3d8762021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575255/?tool=EBIhttps://doaj.org/toc/1932-6203NK2 homeobox 1 (NKX2-1) is a thyroid transcription factor essential for proper thyroid formation and maintaining its physiological function. In thyroid cancer, NKX2-1 expression decreases in parallel with declined differentiation. However, the molecular pathways and mechanisms connecting NKX2-1 to thyroid cancer phenotypes are largely unknown. This study aimed to examine the effects of NKX2-1 re-expression on dedifferentiated thyroid cancer cell death and explore the underlying mechanisms. A human papillary thyroid carcinoma cell line lacking NKX2-1 expression was infected with an adenoviral vector containing Nkx2-1. Cell viability decreased after Nkx2-1 transduction and apoptosis and necrosis were detected. Arginase 2 (ARG2), regulator of G protein signaling 4 (RGS4), and RGS5 mRNA expression was greatly increased in Nkx2-1-transducted cells. After suppressing these genes by siRNA, cell death, apoptosis, and necrosis decreased in RGS4 knockdown cells. These findings demonstrated that cell death was induced via apoptosis and necrosis by NKX2-1 re-expression and involves RGS4.Yuko ItoFumihiko FuruyaKatsumi TakiHideaki SuzukiHiroki ShimuraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yuko Ito
Fumihiko Furuya
Katsumi Taki
Hideaki Suzuki
Hiroki Shimura
NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
description NK2 homeobox 1 (NKX2-1) is a thyroid transcription factor essential for proper thyroid formation and maintaining its physiological function. In thyroid cancer, NKX2-1 expression decreases in parallel with declined differentiation. However, the molecular pathways and mechanisms connecting NKX2-1 to thyroid cancer phenotypes are largely unknown. This study aimed to examine the effects of NKX2-1 re-expression on dedifferentiated thyroid cancer cell death and explore the underlying mechanisms. A human papillary thyroid carcinoma cell line lacking NKX2-1 expression was infected with an adenoviral vector containing Nkx2-1. Cell viability decreased after Nkx2-1 transduction and apoptosis and necrosis were detected. Arginase 2 (ARG2), regulator of G protein signaling 4 (RGS4), and RGS5 mRNA expression was greatly increased in Nkx2-1-transducted cells. After suppressing these genes by siRNA, cell death, apoptosis, and necrosis decreased in RGS4 knockdown cells. These findings demonstrated that cell death was induced via apoptosis and necrosis by NKX2-1 re-expression and involves RGS4.
format article
author Yuko Ito
Fumihiko Furuya
Katsumi Taki
Hideaki Suzuki
Hiroki Shimura
author_facet Yuko Ito
Fumihiko Furuya
Katsumi Taki
Hideaki Suzuki
Hiroki Shimura
author_sort Yuko Ito
title NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
title_short NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
title_full NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
title_fullStr NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
title_full_unstemmed NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
title_sort nkx2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/0c6dd759a1584754b8767fff4bc3d876
work_keys_str_mv AT yukoito nkx21reexpressioninducescelldeaththroughapoptosisandnecrosisindedifferentiatedthyroidcarcinomacells
AT fumihikofuruya nkx21reexpressioninducescelldeaththroughapoptosisandnecrosisindedifferentiatedthyroidcarcinomacells
AT katsumitaki nkx21reexpressioninducescelldeaththroughapoptosisandnecrosisindedifferentiatedthyroidcarcinomacells
AT hideakisuzuki nkx21reexpressioninducescelldeaththroughapoptosisandnecrosisindedifferentiatedthyroidcarcinomacells
AT hirokishimura nkx21reexpressioninducescelldeaththroughapoptosisandnecrosisindedifferentiatedthyroidcarcinomacells
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