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Published on: March 30, 2019
EHMT1 knockdown induces apoptosis and cell cycle arrest in lung cancer cells by increasing CDKN1A expression
Jinkwon Lee1,2, Kwangho Kim1, Tae Young Ryu1
1Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
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.
Insights
EHMT1, a histone methyltransferase, is elevated in lung cancer and drives cancer cell growth. Reducing EHMT1 triggers apoptosis and cell cycle arrest, offering potential therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Histone methyltransferases' roles in human diseases, especially cancer, are not fully understood.
- EHMT1 (EuHMT1/G9a-like protein) is a histone lysine methyltransferase.
- Dysfunctional histone methyltransferases are implicated in various cancers.
Purpose of the Study:
- To investigate the role of EHMT1 in lung cancer pathogenesis.
- To elucidate the molecular mechanisms by which EHMT1 influences cancer cell behavior.
Main Methods:
- Immunohistochemical analysis of EHMT1 expression in lung carcinoma tissues.
- RNA-sequencing (RNA-seq) and Gene Ontology (GO) analysis.
- Flow cytometry (FACS) analysis, cell growth assays, and 3D spheroid culture.
- Gene knockdown experiments targeting EHMT1.
Main Results:
- EHMT1 expression is significantly upregulated in human lung carcinomas compared to normal lung tissues.
- EHMT1 is associated with apoptosis and cell cycle regulation.
- Knockdown of EHMT1 induces apoptosis and G1 cell cycle arrest in lung cancer cell lines (A549, H1299).
- EHMT1 knockdown leads to CDKN1A upregulation and E-cadherin downregulation, affecting cell aggregation in 3D spheroids.
Conclusions:
- EHMT1 plays a critical role in regulating lung cancer cell apoptosis and cell cycle progression.
- EHMT1 modulates CDKN1A expression, impacting cell cycle arrest.
- EHMT1 may serve as a potential therapeutic target for lung cancer treatment.
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