三阴性乳腺癌（TNBC）是一种非常侵袭性的癌症，生长和传播速度快，并且普遍会复发。TNBC的治疗选择有限，仍需要全面探索。报道称，与柠檬酸结合的金纳米颗粒（柠檬酸AuNPs）具有抗癌潜力；然而，它们在调控TNBC中的微小核糖核酸（miRNA）的作用尚未得到研究。本研究通过调控TNBC细胞中的miRNA，研究了柠檬酸AuNPs对肿瘤性炎症的潜力。金纳米颗粒是使用三钠柠檬酸盐法化学合成的，并通过紫外-可见光谱和动态光散射研究进行表征。使用Targetscan生物信息学分析miRNA靶基因。使用TaqMan测定miRNA和mRNA的水平。通过含有整个mRNA 3'端非翻译区（3'UTR）的荧光素酶报告基因克隆进行miRNA的配对验证，进一步通过转染miRNA抑制剂验证结果。新合成的柠檬酸AuNPs非常稳定，平均尺寸为28.3 nm。数据确定hsa-miR155-5p是SOCS1（细胞因子信号抑制因子）表达的直接调节因子，柠檬酸AuNPs通过调控hsa-miR155-5p表达来抑制SOCS1的mRNA/蛋白表达。TNBC MDA-MB-231细胞转染抗-miR155-5p后，SOCS1表达明显增加（p<0.001），而柠檬酸AuNPs处理显著抑制抗-miR155-5p转染诱导的SOCS1表达（p<0.05）。这些结果经过IFN-γ刺激的MDA-MB-231细胞验证。此外，数据还确定柠檬酸AuNPs还抑制了转染抗-hsa-miR155-5p的MDA-MB-231细胞中的IFN-γ诱导的NF-κB p65/p50活化。新合成的柠檬酸AuNPs对TNBC细胞稳定且无毒性。柠檬酸AuNPs通过负调控hsa-miR155-5p，抑制了IFN-γ诱导的SOCS1的mRNA/蛋白表达，并且抑制了MDA-MB-231细胞中的NF-κB p65/50活性。这些有关柠檬酸AuNPs在IFN-γ刺激的TNBC细胞中对炎症的抑制作用的新药理机制，提供了AuNPs通过调控miRNA表达来抑制TNBC细胞中的IFN-γ诱导炎症的见解。版权所有©2023 Farhana、Alsrhani、Rasheed和Rasheed。

Triple-negative breast cancer (TNBC) is a very aggressive form of cancer that grows and spreads very fast and generally relapses. Therapeutic options of TNBC are limited and still need to be explored completely. Gold nanoparticles conjugated with citrate (citrate-AuNPs) are reported to have anticancer potential; however, their role in regulating microRNAs (miRNAs) in TNBC has never been investigated. This study investigated the potential of citrate-AuNPs against tumorigenic inflammation via modulation of miRNAs in TNBC cells.Gold nanoparticles were chemically synthesized using the trisodium-citrate method and were characterized by UV-Vis spectrophotometry and dynamic light scattering studies. Targetscan bioinformatics was used to analyze miRNA target genes. Levels of miRNA and mRNA were quantified using TaqMan assays. The pairing of miRNA in 3'untranslated region (3'UTR) of mRNA was validated by luciferase reporter clone, containing the entire 3'UTR of mRNA, and findings were further re-validated via transfection with miRNA inhibitors.Newly synthesized citrate-AuNPs were highly stable, with a mean size was 28.3 nm. The data determined that hsa-miR155-5p is a direct regulator of SOCS1 (suppressor-of-cytokine-signaling) expression and citrate-AuNPs inhibits SOCS1 mRNA/protein expression via modulating hsa-miR155-5p expression. Transfection of TNBC MDA-MB-231 cells with anti-miR155-5p markedly increased SOCS1 expression (p<0.001), while citrate-AuNPs treatment significantly inhibited anti-miR155-5p transfection-induced SOCS1 expression (p<0.05). These findings were validated by IFN-γ-stimulated MDA-MB-231 cells. Moreover, the data also determined that citrate-AuNPs also inhibit IFN-γ-induced NF-κB p65/p50 activation in MDA-MB-231 cells transfected with anti-hsa-miR155-5p.Newly generated citrate-AuNPs were stable and non-toxic to TNBC cells. Citrate-AuNPs inhibit IFN-γ-induced SOCS1 mRNA/protein expression and deactivate NF-κB p65/50 activity via negative regulation of hsa-miR155-5p. These novel pharmacological actions of citrate-AuNPs on IFN-γ-stimulated TNBC cells provide insights that AuNPs inhibit IFN-γ induced inflammation in TNBC cells by modulating the expression of microRNAs.Copyright © 2023 Farhana, Alsrhani, Rasheed and Rasheed.