EHMT1 knockdown induces apoptosis and cell cycle arrest in lung cancer cells by increasing CDKN1A expression.

Abstract

Dozens of histone methyltransferases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human diseases such as cancer remain largely unclear. Here, we demonstrate the involvement of EHMT1, a histone lysine methyltransferase, in lung cancer. Immunohistochemical analysis indicated that the expression levels of EHMT1 are significantly elevated in human lung carcinomas compared with non-neoplastic lung tissues. Through gene ontology analysis of RNA-seq results, we showed that EHMT1 is clearly associated with apoptosis and the cell cycle process. Moreover, FACS analysis and cell growth assays showed that knockdown of EHMT1 induced apoptosis and G1 cell cycle arrest via upregulation of CDKN1A in A549 and H1299 cell lines. Finally, in 3D spheroid culture, compared to control cells, EHMT1 knockdown cells exhibited reduced aggregation of 3D spheroids and clear upregulation of CDKN1A and downregulation of E-cadherin. Therefore, the results of the present study suggest that EHMT1 plays a critical role in the regulation of cancer cell apoptosis and the cell cycle by modulating CDKN1A expression. Further functional analyses of EHMT1 in the context of human tumorigenesis may aid in the development of novel therapeutic strategies for cancer.

• Authors: Jinkwon Lee, Kwangho Kim, Tae Young Ryu, Cho-Rok Jung, Moo-Seung Lee, Jung Hwa Lim, Kunhyang Park, Dae-Soo Kim, Mi-Young Son, Ryuji Hamamoto, Hyun-Soo Cho
• Journal: Molecular oncology (Mol Oncol) Vol. 15 Issue 11 Pg. 2989-3002 (11 2021) ISSN: 1878-0261 [Electronic] United States
• PMID: 34214254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• EHMT1 protein, human
• Histone-Lysine N-Methyltransferase

Topics

• Apoptosis (genetics)
• Cell Cycle
• Cell Cycle Checkpoints (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Histone-Lysine N-Methyltransferase (genetics, metabolism)
• Humans
• Lung (pathology)
• Lung Neoplasms (genetics, pathology)