The suppression of Set7/9 methyltransferase leads to the metabolic reprogramming of lung cancer cells

다국어 초록 (Multilingual Abstract)

Set7/9 is the histone and non‐histone lysine methyltransferase that targets histones H1, H3 and a number of proteins playing principle role in cell proliferation, cancer progression and DNA damage response, such as p53, PARP1, E2F1 and others. In the frame of this study, we suggested that Set7/9 may contribute to cancel cell metabolism regulation and participate in tumor transformation.
We have tested human non‐small cell lung cancer (NSCLC) cell lines H1299, A549 and H1975 with knock‐down of Set7/9 for the proliferation rate and showed that Set7/9 suppression leads to increase of proliferation of tested cell lines. As a result of cell cycle analysis, we demonstrated that Set7/9 inhibition or ablation results in increase of S phase population that is consistent with proliferation tests data.
Assuming that Set7/9 may affect the metabolic status NSCLC cells, we analyzed the mitochondrial membrane potential of H1299, A549 and H1975 cells with different status of this enzyme. We demonstrated that cells with suppressed Set7/9 level are characterized by the increased mitochondrial membrane potential.
Next, we tested the effect of Set7/9 on glycolytic enzymes level both on mRNA and protein level. We showed that Set7/9 suppression results in elevation of key glycolytic enzymes – lactate dehydrogenase LDHA, aldolase AldoA, hexokinase (HK2) as well as glucose transporter (Glut1), that explains the effect of Set7/9 on cell proliferation rate. To summarize this study, we have shown that Set7/9 methyltransferase acts as restraining factor for NSCLC cells proliferation, and suppression of Set7/9 causes the glycolysis activation and contributes to cancer‐associated phenotype formation.