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G9a, an Epigenetic Modifier, Affects Cell Viability and Serine‐Glycine Synthesis Pathway by Altering ATF4 Expression
Author(s) -
Kim HaEun,
Park Yoon Jung
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb331
Subject(s) - histone methyltransferase , biology , epigenetics , lung cancer , cancer research , gene silencing , cancer , cancer cell , biochemistry , gene , medicine , genetics
Lung cancer is the number one cause of cancer deaths in both men and women in worldwide and non‐small‐cell lung cancer (NSCLC) is the most common type of lung cancer. G9a is the eukaryotic histone methyltransferase that contributes to transcriptional silencing of tumor suppressor genes by modulating histone 3 lysine 9 (H3K9) methylation. Recent studies have highlighted it has a crucial function in breast cancer and neuroblastoma via affecting serine‐glycine synthesis pathway (SSP), which provides the essential precursors for the synthesis of proteins, nucleic acids, and lipids. However, few studies have addressed the role of G9a regulation in lung cancer. Here, we confirm that G9a expression in NSCLC, especially squamous cell cancer (SCC), is higher than normal through a secondary analysis using Oncomine and quantitative analysis on patient samples. H1299, an aggressive lung cancer cell line, shows higher level of G9a expression than A549, another commonly used cell line. Inhibition of G9a by BIX01294 (BIX; a G9a specific inhibitor) results in suppression of cell proliferation in both cell lines. In addition, we show that the reduction of G9a expression by small interfering RNA causes cell death. To see the regulation of G9a on SSP, we access four SSP enzyme genes encoding PHGDH, PSAT1, SHMT1, and SHMT2. Unlike the results from other studies, treatment of BIX increases mRNA expression of SSP enzymes, PSAT1 and SHMT2, in the high level of the treatment. Furthermore, BIX‐treated cells show the increase of ATF4 mRNA expression, which is the key regulator of amino acid synthesis, in the same concentration. In summary, our results demonstrate that G9a is upregulated in NSCLC and inhibition of G9a reduces cell viability. Moreover, G9a alters transcriptional levels of SSP enzyme genes through upregulating ATF4. A further study is needed to show a mechanism underlying interplay between ATF4 and G9a.