Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells
MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanopart...
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1404 |
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| author | Aisha Farhana Abdullah Alsrhani Ruqaih S. Alghsham Wassila Derafa Yusuf Saleem Khan Zafar Rasheed |
| author_facet | Aisha Farhana Abdullah Alsrhani Ruqaih S. Alghsham Wassila Derafa Yusuf Saleem Khan Zafar Rasheed |
| author_sort | Aisha Farhana |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanoparticles (GNP) against IL-6 overexpression and the modulation of miRNA-26a-5p in breast cancer (BC) cells. GNP were synthesized using the trisodium citrate method and characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). To predict the binding of miR-26a-5p in the IL-6 mRNA’s 3′UTR, we utilized bioinformatics algorithms. Luciferase reporter clone assays and anti-miRNA-26a-5p transfection were employed to validate the binding of miR26a-5p in the IL-6 mRNA’s 3′UTR. The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082. The synthesized GNP were spherical with a mean size of 28.3 nm, exhibiting high stability, and were suitable for BC cell treatment. We found that miR-26a-5p directly regulated IL-6 overexpression in MCF-7 cells activated with PMA. Treatment of MCF-7 cells with GNP resulted in the inhibition of IL-6 overexpression and secretion through the increase of miR26a-5p. Furthermore, GNP deactivated NF-κBp65/NF-κBp50 transcription activity. The newly engineered GNP demonstrated safety and showed promise as a therapeutic approach for reducing IL-6 overexpression. The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways. |
| first_indexed | 2024-03-08T03:56:53Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:56:53Z |
| publishDate | 2024-01-01 |
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| spelling | doaj.art-9a38e7bfea964a6d99ec6b8bc4f3a0d32024-02-09T15:13:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253140410.3390/ijms25031404Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer CellsAisha Farhana0Abdullah Alsrhani1Ruqaih S. Alghsham2Wassila Derafa3Yusuf Saleem Khan4Zafar Rasheed5Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pathology, College of Medicine, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Chemistry, College of Science, Jouf University, Aljouf 72388, Saudi ArabiaDepartment of Anatomy, College of Medicine, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pathology, College of Medicine, Qassim University, Buraidah 51452, Saudi ArabiaMicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known to promote cancer progression and treatment resistance. In this study, we aimed to explore the therapeutic effects of gold nanoparticles (GNP) against IL-6 overexpression and the modulation of miRNA-26a-5p in breast cancer (BC) cells. GNP were synthesized using the trisodium citrate method and characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). To predict the binding of miR-26a-5p in the IL-6 mRNA’s 3′UTR, we utilized bioinformatics algorithms. Luciferase reporter clone assays and anti-miRNA-26a-5p transfection were employed to validate the binding of miR26a-5p in the IL-6 mRNA’s 3′UTR. The activity of RelA and NF-κBp50 was assessed and confirmed using Bay 11-7082. The synthesized GNP were spherical with a mean size of 28.3 nm, exhibiting high stability, and were suitable for BC cell treatment. We found that miR-26a-5p directly regulated IL-6 overexpression in MCF-7 cells activated with PMA. Treatment of MCF-7 cells with GNP resulted in the inhibition of IL-6 overexpression and secretion through the increase of miR26a-5p. Furthermore, GNP deactivated NF-κBp65/NF-κBp50 transcription activity. The newly engineered GNP demonstrated safety and showed promise as a therapeutic approach for reducing IL-6 overexpression. The GNP suppressed IL-6 overexpression and secretion by deactivating NF-κBp65/NF-κBp50 transcription activity and upregulating miR-26a-5p expression in activated BC cells. These findings suggest that GNP have potential as a therapeutic intervention for BC by targeting IL-6 expression and associated pathways.https://www.mdpi.com/1422-0067/25/3/1404BCGNPgold nanoparticlesmicroRNARelAIL-6 |
| spellingShingle | Aisha Farhana Abdullah Alsrhani Ruqaih S. Alghsham Wassila Derafa Yusuf Saleem Khan Zafar Rasheed Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells International Journal of Molecular Sciences BC GNP gold nanoparticles microRNA RelA IL-6 |
| title | Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells |
| title_full | Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells |
| title_fullStr | Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells |
| title_full_unstemmed | Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells |
| title_short | Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells |
| title_sort | gold nanoparticles downregulate il 6 expression production by upregulating microrna 26a 5p and deactivating the rela and nf κbp50 transcription pathways in activated breast cancer cells |
| topic | BC GNP gold nanoparticles microRNA RelA IL-6 |
| url | https://www.mdpi.com/1422-0067/25/3/1404 |
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