2. Academic Validation
  3. Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis

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

  • Exp Mol Med. 2023 May 1. doi: 10.1038/s12276-023-00987-1.
Kwangho Kim # 1 2,  Tae Young Ryu # 1,  Eunsun Jung # 1,  Tae-Su Han # 1 3 4,  Jinkwon Lee 1 3,  Seon-Kyu Kim 1,  Yu Na Roh 1 3,  Moo-Seung Lee 1,  Cho-Rok Jung 1 3,  Jung Hwa Lim 1,  Ryuji Hamamoto 5,  Hye Won Lee 6,  Keun Hur 7,  Mi-Young Son 8 9 10,  Dae-Soo Kim 11 12,  Hyun-Soo Cho 13 14 15
Affiliations

Affiliations

  • 1 Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • 2 College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
  • 3 Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea.
  • 4 Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
  • 5 Division of Molecular Modification and Cancer Biology, National Cancer Center, Tokyo, Japan.
  • 6 Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea.
  • 7 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. [email protected].
  • 8 Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. [email protected].
  • 9 Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea. [email protected].
  • 10 Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea. [email protected].
  • 11 Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. [email protected].
  • 12 Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea. [email protected].
  • 13 Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. [email protected].
  • 14 Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea. [email protected].
  • 15 Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea. [email protected].
  • # Contributed equally.
PMID: 37121971 DOI: 10.1038/s12276-023-00987-1
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.

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