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

• Published in: International journal of molecular sciences 2024-02, Vol.25 (3), p.1404
• Main Authors: Farhana, Aisha, Alsrhani, Abdullah, Alghsham, Ruqaih S, Derafa, Wassila, Khan, Yusuf Saleem, Rasheed, Zafar
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer; Cancer therapies; Care and treatment; Cell culture; Cell growth; Cytokines; Cytotoxicity; Development and progression; Genetic transcription; GNP; gold nanoparticles; Health aspects; IL-6; Interleukins; Medical prognosis; Medical research; MicroRNA; MicroRNAs; Nanoparticles; Proteins; RelA; Spectrum analysis; Toxicity; Treatment resistance
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25031404

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.