Gold Nanoparticles Inhibit PMA-Induced MMP-9 Expression via microRNA-204-5p Upregulation and Deactivation of NF-κBp65 in Breast Cancer Cells

• Published in: Biology (Basel, Switzerland) Switzerland), 2023-05, Vol.12 (6), p.777
• Main Authors: Farhana, Aisha, Alsrhani, Abdullah, Nazam, Nazia, Ullah, Muhammad Ikram, Khan, Yusuf Saleem, Rasheed, Zafar
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Bioinformatics; Brain cancer; Breast cancer; Cancer cells; Cell activation; Deactivation; Electron microscopes; Epigenetics; Gelatin; Gelatinase B; Gene expression; Gold; gold nanoparticles; Health aspects; hsa-miR-204-5p; Malignancy; Matrix metalloproteinase; Metalloproteinase; MicroRNA; MicroRNAs; miRNA; MMP-9; Nanoparticles; NF-κB protein; NF-κBp65; parthenolide; Protein binding; Proteins; Scanning electron microscopy; Transcription activation; Transfection; Transmission electron microscopy; Up-regulation; Zeta potential
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12060777

Breast cancer (BC) is the most common malignancy in females globally. Matrix metalloproteinase-9 (MMP-9) is crucial to the invasion, progression and spread of BC. Gold nanoparticles (AuNPs) have an anti-tumorigenic role, but their therapeutic role in microRNAs (miRNAs) regulation has not been explored. This study determined the potential of AuNPs against MMP-9 overexpression/production and miRNA-204-5p regulation in BC cells. AuNPs were newly engineered, and their stability was analyzed using the zeta potential, polydispersity index, surface-plasmon-resonance peak and transmission electron microscopy. A bioinformatics algorithm was used to predict the pairing of miRNA in the 3'untranslated-region (3'UTR) of MMP-9 mRNA. TaqMan assays were carried out to quantify miRNA and mRNA, whereas MMP-9-specific immunoassays and gelatin zymography were used to determine protein secretion and activity. The binding of miRNA in MMP-9 mRNA 3'UTR was verified by luciferase reporter clone assays and transfection with anti-miRNAs. In addition, NF-κBp65 activity was determined and confirmed with parthenolide treatment. Engineered AuNPs were highly stable and spherical in shape, with a mean size of 28.3 nm. Tested in MCF-7 BC cells, microRNA-204-5p directly regulates MMP-9. AuNPs inhibit PMA-induced MMP-9 mRNA and protein via hsa-miR-204-5p upregulation. Anti-miR-204 transfected MCF-7 cells demonstrated enhanced MMP-9 expression ( < 0.001), while AuNPs treatment attenuated MMP-9 expression in a dose-dependent manner ( < 0.05). Moreover, AuNPs also inhibit PMA-induced NF-κBp65 activation in anti-hsa-miR-204 transfected MCF-7 cells. Engineered AuNPs were stable and non-toxic to BC cells. AuNPs inhibit PMA-induced MMP-9 expression, production and activation via NF-κBp65 deactivation and hsa-miR-204-5p upregulation. These novel therapeutic potentials of AuNPs on stimulated BC cells provide novel suggestions that AuNPs inhibit carcinogenic activity via inverse regulation of microRNAs.