G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely relate...

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Main Authors: Yunho Jin, Shinji Park, Soon-Yong Park, Chae-Young Lee, Da-Young Eum, Jae-Woong Shim, Si-Ho Choi, Yoo-Jin Choi, Seong-Joon Park, Kyu Heo
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/2/589
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author Yunho Jin
Shinji Park
Soon-Yong Park
Chae-Young Lee
Da-Young Eum
Jae-Woong Shim
Si-Ho Choi
Yoo-Jin Choi
Seong-Joon Park
Kyu Heo
author_facet Yunho Jin
Shinji Park
Soon-Yong Park
Chae-Young Lee
Da-Young Eum
Jae-Woong Shim
Si-Ho Choi
Yoo-Jin Choi
Seong-Joon Park
Kyu Heo
author_sort Yunho Jin
collection DOAJ
description Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-β superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.
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spelling doaj.art-8d10906420494f359373855252c12b1b2023-11-23T14:00:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123258910.3390/ijms23020589G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast CancerYunho Jin0Shinji Park1Soon-Yong Park2Chae-Young Lee3Da-Young Eum4Jae-Woong Shim5Si-Ho Choi6Yoo-Jin Choi7Seong-Joon Park8Kyu Heo9Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaResearch Center, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, KoreaEpigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-β superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.https://www.mdpi.com/1422-0067/23/2/589breast cancerepigeneticsG9aBMP5
spellingShingle Yunho Jin
Shinji Park
Soon-Yong Park
Chae-Young Lee
Da-Young Eum
Jae-Woong Shim
Si-Ho Choi
Yoo-Jin Choi
Seong-Joon Park
Kyu Heo
G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
International Journal of Molecular Sciences
breast cancer
epigenetics
G9a
BMP5
title G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
title_full G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
title_fullStr G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
title_full_unstemmed G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
title_short G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer
title_sort g9a knockdown suppresses cancer aggressiveness by facilitating smad protein phosphorylation through increasing bmp5 expression in luminal a type breast cancer
topic breast cancer
epigenetics
G9a
BMP5
url https://www.mdpi.com/1422-0067/23/2/589
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