Activation of Hypoxia Inducible Factor-1 Alpha-Mediated DNA Methylation Enzymes (DNMT3a and TET2) Under Hypoxic Conditions Regulates S100A6 Transcription to Promote Lung Cancer Cell Growth and Metastasis
Aims: This research was aimed at investigating the effects of hypoxia inducible factor-1 alpha (HIF-1α)-mediated DNA methylation enzymes (ten-eleven translocase-2 [TET2] and DNA methyltransferase-3a [DNMT3a]) under hypoxic conditions on S100A6 transcription, thereby promoting the growth and metastasis of lung cancer cells. Methods: The expression of HIF-1α or S100A6 in lung cancer cells was interfered with under normoxic and hypoxic conditions, and the cell proliferative, migratory, and invasive properties were assessed. The mechanism of HIF-1α-regulated TET2 and DNMT3 effects on S100A6 transcription under hypoxic conditions was further investigated. Results: Functionally, S100A6 over-expression promoted lung cancer cell proliferation and metastasis. S100A6 over-expression reversed the inhibitory effects of HIF-1α interference on the proliferation and metastasis of lung cancer cells. S100A6 was induced to express in an HIF-1α-dependent manner under hypoxic conditions, and silencing S100A6 or HIF-1α suppressed lung cancer cell proliferation and metastasis under hypoxic conditions. Further, The Cancer Genome Atlas-lung adenocarcinoma database analysis revealed that S100A6 mRNA levels had a negative correlation with methylation levels. Mechanistically, CpG hypomethylation status in the S100A6 promoter hypoxia response element had an association with HIF-1α induction. TET2 was enriched in S100A6 promoter region of lung cancer cells under hypoxic conditions, whereas DNMT3a enrichment was reduced in S100A6 promoter region. HIF-1α-mediated S100A6 activation was linked to DNMT3a-associated epigenetic inactivation and TET2 activation. Innovation: The activation of HIF-1α-mediated DNA methylation enzymes under hypoxic conditions regulated S100A6 transcription, thereby promoting lung cancer cell growth and metastasis. Conclusion: In lung cancer progression, hypoxia-induced factor HIF-1α combined with DNA methylation modifications co-regulates S100A6 transcriptional activation and promotes lung cancer cell growth and metastasis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Antioxidants & redox signaling - (2024) vom: 18. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Tengfei [VerfasserIn] |
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| Links: |
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| Themen: |
DNA methylation |
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| Anmerkungen: |
Date Revised 19.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1089/ars.2023.0397 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367888548 |
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| 245 | 1 | 0 | |a Activation of Hypoxia Inducible Factor-1 Alpha-Mediated DNA Methylation Enzymes (DNMT3a and TET2) Under Hypoxic Conditions Regulates S100A6 Transcription to Promote Lung Cancer Cell Growth and Metastasis |
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| 520 | |a Aims: This research was aimed at investigating the effects of hypoxia inducible factor-1 alpha (HIF-1α)-mediated DNA methylation enzymes (ten-eleven translocase-2 [TET2] and DNA methyltransferase-3a [DNMT3a]) under hypoxic conditions on S100A6 transcription, thereby promoting the growth and metastasis of lung cancer cells. Methods: The expression of HIF-1α or S100A6 in lung cancer cells was interfered with under normoxic and hypoxic conditions, and the cell proliferative, migratory, and invasive properties were assessed. The mechanism of HIF-1α-regulated TET2 and DNMT3 effects on S100A6 transcription under hypoxic conditions was further investigated. Results: Functionally, S100A6 over-expression promoted lung cancer cell proliferation and metastasis. S100A6 over-expression reversed the inhibitory effects of HIF-1α interference on the proliferation and metastasis of lung cancer cells. S100A6 was induced to express in an HIF-1α-dependent manner under hypoxic conditions, and silencing S100A6 or HIF-1α suppressed lung cancer cell proliferation and metastasis under hypoxic conditions. Further, The Cancer Genome Atlas-lung adenocarcinoma database analysis revealed that S100A6 mRNA levels had a negative correlation with methylation levels. Mechanistically, CpG hypomethylation status in the S100A6 promoter hypoxia response element had an association with HIF-1α induction. TET2 was enriched in S100A6 promoter region of lung cancer cells under hypoxic conditions, whereas DNMT3a enrichment was reduced in S100A6 promoter region. HIF-1α-mediated S100A6 activation was linked to DNMT3a-associated epigenetic inactivation and TET2 activation. Innovation: The activation of HIF-1α-mediated DNA methylation enzymes under hypoxic conditions regulated S100A6 transcription, thereby promoting lung cancer cell growth and metastasis. Conclusion: In lung cancer progression, hypoxia-induced factor HIF-1α combined with DNA methylation modifications co-regulates S100A6 transcriptional activation and promotes lung cancer cell growth and metastasis | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a proliferation | |
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| 700 | 1 | |a Wang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Mengxue |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Kemeng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, La |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Geng, Yuliu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lili |e verfasserin |4 aut | |
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