Regulating Tumor N 6 ‐Methyladenosine Methylation Landscape using Hypoxia‐Modulating OsS x Nanoparticles
| Autor: | Yuyi Ling, Hongsheng Wang, Cai-Ping Tan, Zong-Wan Mao, Yue Zheng, Hang Zhang, Liang-Nian Ji, Dong-Yang Zhang, Gang-Gang Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Regulation of gene expression
Methyltransferase Tumor hypoxia RNA methylation technology industry and agriculture RNA 02 engineering and technology General Chemistry Methylation 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences Cell biology Biomaterials chemistry.chemical_compound chemistry General Materials Science Hypoxia Pathway N6-Methyladenosine 0210 nano-technology Biotechnology |
| Zdroj: | Small. 17:2005086 |
| ISSN: | 1613-6829 1613-6810 |
| DOI: | 10.1002/smll.202005086 |
| Popis: | The epigenetic dysregulation and hypoxia are two important factors that drive tumor malignancy, and N6 -methyladenosine (m6 A) in mRNA is involved in the regulation of gene expression. Herein, a nanocatalyst OsSx -PEG (PEG = poly(ethylene glycol)) nanoparticles (NPs) as O2 modulator is developed to improve tumor hypoxia. OsSx -PEG NPs can significantly downregulate genes involved in hypoxia pathway. Interestingly, OsSx -PEG NPs elevate RNA m6 A methylation levels to cause the m6 A-dependent mRNA degradation of the hypoxia-related genes. Moreover, OsSx -PEG NPs can regulate the expression of RNA m6 A methyltransferases and demethylases. Finally, DOX@OsSx -PEG (DOX = doxorubicin; utilized as a model drug) NPs modulate tumor hypoxia and regulate mRNA m6 A methylation of hypoxia-related genes in vivo. As the first report about relationship between catalytic nanomaterials and RNA modifications, the research opens a new avenue for unveiling the underlying action mechanisms of hypoxia-modulating nanomaterials and shows potential of regulating RNA modification to overcome chemoresistance. |
| Databáze: | OpenAIRE |
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