|
KMID : 0620920230550050952
|
|
Experimental & Molecular Medicine
2023 Volume.55 No. 5 p.952 ~ p.964
|
|
|
Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis
|
|
Kim Kwang-Ho
Ryu Tae-Young
Jung Eun-Sun
Han Tae-Su
Lee Jin-Kwon
Kim Seon-Kyu
Manaf Al-Hashimi
Lee Moo-Seung
Jung Cho-Rok
Lim Jung-Hwa
Ryuji Hamamoto
Lee Hye-Won
Hur Keun
Son Mi-Young
Kim Dae-Soo
Cho Hyun-Soo
|
|
|
Abstract
|
|
|
|
Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment.
|
|
|
KEYWORD
|
|
|
Gene silencing, Lung cancer, Metastasis
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|