Open AccessNKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells
Author(s) -
Yuko Ito,
Fumihiko Furuya,
Katsumi Taki,
Hideaki Suzuki,
Hiroki Shimura
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259558
Subject(s) - apoptosis , gene knockdown , programmed cell death , thyroid cancer , cancer research , necrosis , biology , viability assay , thyroid carcinoma , tumor necrosis factor alpha , microbiology and biotechnology , thyroid , endocrinology , genetics
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.