p53-independent effects of Set7/9 lysine methyltransferase on metabolism of non-small cell lung cancer cells
Open accessAbstract
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.
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Different oncogenes and oncosuppressors have a critical impact on these metabolic pathways.
“Different oncogenes and oncosupressors have a critical impact on these metabolic pathways [20,40,46,47,75,76].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [76]
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Cường, N. M., Fefilova, E., Loc, V. T., Karpova, N. S., Ha, N. X., Daks, A. A., Ha, N. V., Hương, T. T., Parfenyev, S. E., Nazarov, A., et al. (2026) · Pharmaceuticals · doi:10.3390/ph19060814
- Authors
- Daks, A., Shuvalov, O., Fedorova, O., Petukhov, A., Lezina, L., Zharova, A., Baidyuk, E., Khudiakov, A., & Barlev, N. A.
- Affiliations
- Russian Academy of Sciences (RU)
- Moscow Institute of Physics and Technology (RU)
- Corresponding author
- Barlev, Nickolai A.
- ORCID
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2021-10-06
- Volume
- 11
- Pages
- 706668-706668
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC8528242
- OpenAlex
- W3204889378
- Cited by
- 15
- References
- 65
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 1
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Russian Science Foundation
- Ministry of Science and Higher Education of the Russian Federation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SET7/9, lysine methyltransferase, non-small cell lung cancer, cancer metabolism, c-Myc, glycolysis, HK2, LDHA, aldolase B, GLUT1, HIF1A, mitochondrial membrane potential, p53-independent regulation, energy metabolism, patient survival
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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