Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis

Kwangho Kim; Tae Young Ryu; Eunsun Jung; Tae Su Han; Jinkwon Lee; Seon Kyu Kim; Yu Na Roh; Moo Seung Lee; Cho Rok Jung; Jung Hwa Lim; Ryuji Hamamoto; Hye Won Lee; Keun Hur; Mi Young Son; Dae Soo Kim; Hyun Soo Cho

doi:10.1038/s12276-023-00987-1

Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis

Kwangho Kim, Tae Young Ryu, Eunsun Jung, Tae Su Han, Jinkwon Lee, Seon Kyu Kim, Yu Na Roh, Moo Seung Lee, Cho Rok Jung, Jung Hwa Lim, Ryuji Hamamoto, Hye Won Lee, Keun Hur, Mi Young Son, Dae Soo Kim, Hyun Soo Cho

Department of Medicine

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	952-964
Number of pages	13
Journal	Experimental and Molecular Medicine
Volume	55
Issue number	5
DOIs	https://doi.org/10.1038/s12276-023-00987-1
State	Published - May 2023

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Kim, K., Ryu, T. Y., Jung, E., Han, T. S., Lee, J., Kim, S. K., Roh, Y. N., Lee, M. S., Jung, C. R., Lim, J. H., Hamamoto, R., Lee, H. W., Hur, K., Son, M. Y., Kim, D. S., & Cho, H. S. (2023). Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis. Experimental and Molecular Medicine, 55(5), 952-964. https://doi.org/10.1038/s12276-023-00987-1

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title = "Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis",

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.",

author = "Kwangho Kim and Ryu, {Tae Young} and Eunsun Jung and Han, {Tae Su} and Jinkwon Lee and Kim, {Seon Kyu} and Roh, {Yu Na} and Lee, {Moo Seung} and Jung, {Cho Rok} and Lim, {Jung Hwa} and Ryuji Hamamoto and Lee, {Hye Won} and Keun Hur and Son, {Mi Young} and Kim, {Dae Soo} and Cho, {Hyun Soo}",

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year = "2023",

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doi = "10.1038/s12276-023-00987-1",

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AU - Kim, Kwangho

AU - Ryu, Tae Young

AU - Jung, Eunsun

AU - Han, Tae Su

AU - Lee, Jinkwon

AU - Kim, Seon Kyu

AU - Roh, Yu Na

AU - Lee, Moo Seung

AU - Jung, Cho Rok

AU - Lim, Jung Hwa

AU - Hamamoto, Ryuji

AU - Lee, Hye Won

AU - Hur, Keun

AU - Son, Mi Young

AU - Kim, Dae Soo

AU - Cho, Hyun Soo

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

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Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis

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