p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells
Set7/9 is a lysine-specific methyltransferase, which regulates the functioning of both the histone and non-histone substrates, thereby significantly affecting the global gene expression landscape. Using microarray expression profiling, we have identified several key master regulators of metabolic ne...
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doaj-bc54fb5f2736430f844f7e22be76c70b2021-10-06T06:30:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.706668706668p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer CellsAlexandra Daks0Oleg Shuvalov1Olga Fedorova2Alexey Petukhov3Alexey Petukhov4Larissa Lezina5Arsenia Zharova6Ekaterina Baidyuk7Alexander Khudiakov8Nickolai A. Barlev9Nickolai A. Barlev10Institute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Molecular Biology and Genetics, Almazov National Medical Research Centre, St Petersburg, RussiaRegulation of Cell Signaling Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaInstitute of Molecular Biology and Genetics, Almazov National Medical Research Centre, St Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences, St Petersburg, RussiaRegulation of Cell Signaling Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny, RussiaSet7/9 is a lysine-specific methyltransferase, which regulates the functioning of both the histone and non-histone substrates, thereby significantly affecting the global gene expression landscape. Using microarray expression profiling, we have identified several key master regulators of metabolic networks, including c-Myc, that were affected by Set7/9 status. Consistent with this observation, c-Myc transcriptional targets—genes encoding the glycolytic enzymes hexokinase (HK2), aldolase (ALDOB), and lactate dehydrogenase (LDHA)—were upregulated upon Set7/9 knockdown (Set7/9KD). Importantly, we showed the short hairpin RNA (shRNA)-mediated attenuation of Set7/9 augmented c-Myc, GLUT1, HK2, ALDOA, and LDHA expression in non-small cell lung cancer (NSCLC) cell lines, not only at the transcriptional but also at the protein level. In line with this observation, Set7/9KD significantly augmented the membrane mitochondrial potential (MMP), glycolysis, respiration, and the proliferation rate of NSCLC cells. Importantly, all these effects of Set7/9 on cell metabolism were p53-independent. Bioinformatic analysis has shown a synergistic impact of Set7/9 together with either GLUT1, HIF1A, HK2, or LDHA on the survival of lung cancer patients. Based on these evidence, we hypothesize that Set7/9 can be an important regulator of energy metabolism in NSCLC.https://www.frontiersin.org/articles/10.3389/fonc.2021.706668/fullSet7/9SETD7non-small cell lung cancer (NSCLC)glycolysismetabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandra Daks Oleg Shuvalov Olga Fedorova Alexey Petukhov Alexey Petukhov Larissa Lezina Arsenia Zharova Ekaterina Baidyuk Alexander Khudiakov Nickolai A. Barlev Nickolai A. Barlev |
spellingShingle |
Alexandra Daks Oleg Shuvalov Olga Fedorova Alexey Petukhov Alexey Petukhov Larissa Lezina Arsenia Zharova Ekaterina Baidyuk Alexander Khudiakov Nickolai A. Barlev Nickolai A. Barlev p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells Frontiers in Oncology Set7/9 SETD7 non-small cell lung cancer (NSCLC) glycolysis metabolism |
author_facet |
Alexandra Daks Oleg Shuvalov Olga Fedorova Alexey Petukhov Alexey Petukhov Larissa Lezina Arsenia Zharova Ekaterina Baidyuk Alexander Khudiakov Nickolai A. Barlev Nickolai A. Barlev |
author_sort |
Alexandra Daks |
title |
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells |
title_short |
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells |
title_full |
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells |
title_fullStr |
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells |
title_full_unstemmed |
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells |
title_sort |
p53-independent effects of set7/9 lysine methyltransferase on metabolism of non-small cell lung cancer cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-10-01 |
description |
Set7/9 is a lysine-specific methyltransferase, which regulates the functioning of both the histone and non-histone substrates, thereby significantly affecting the global gene expression landscape. Using microarray expression profiling, we have identified several key master regulators of metabolic networks, including c-Myc, that were affected by Set7/9 status. Consistent with this observation, c-Myc transcriptional targets—genes encoding the glycolytic enzymes hexokinase (HK2), aldolase (ALDOB), and lactate dehydrogenase (LDHA)—were upregulated upon Set7/9 knockdown (Set7/9KD). Importantly, we showed the short hairpin RNA (shRNA)-mediated attenuation of Set7/9 augmented c-Myc, GLUT1, HK2, ALDOA, and LDHA expression in non-small cell lung cancer (NSCLC) cell lines, not only at the transcriptional but also at the protein level. In line with this observation, Set7/9KD significantly augmented the membrane mitochondrial potential (MMP), glycolysis, respiration, and the proliferation rate of NSCLC cells. Importantly, all these effects of Set7/9 on cell metabolism were p53-independent. Bioinformatic analysis has shown a synergistic impact of Set7/9 together with either GLUT1, HIF1A, HK2, or LDHA on the survival of lung cancer patients. Based on these evidence, we hypothesize that Set7/9 can be an important regulator of energy metabolism in NSCLC. |
topic |
Set7/9 SETD7 non-small cell lung cancer (NSCLC) glycolysis metabolism |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.706668/full |
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