Integrated proteomic profiling and in silico miRNA and lncRNA analysis of glucose-capped fisetin silver nanoparticle-mediated cell proliferation arrest in breast cancer
摘要
Breast cancer remains the most common cancer among women and a major cause of mortality. Fisetin, a natural compound, has demonstrated anti-cancer activity, but its limited bioavailability reduces its therapeutic effect. To overcome this, glucose-capped fisetin silver nanoparticles (GF-Ag NPs) were synthesised, and their significant impact on the MDA-MB-231 breast cancer cell line is reported. This study focused on the proteomic profiling of GF-Ag NP-treated MDA-MB-231 cells using two-dimensional gel electrophoresis and mass spectrometry, which identified 25 proteins with altered expression. Gene ontology and protein-protein interaction analyses indicated these proteins are involved in critical biological and molecular processes. Four key proteins—Nucleolin (NCL), Tropomyosin alpha-4 chain (TPM4), L-lactate dehydrogenase A (LDHA), and Peroxiredoxin-1 (PRDX1)—were chosen for further validation through qRT-PCR based on their relevance to cancer progression. Additionally, bioinformatic prediction tools identified several miRNAs (such as miR-577, miR-205-5p, miR-613, miR-206, and miR-374b-5p) and associated lncRNAs as regulators of these proteins. These results suggest that GF-Ag NPs can modulate the expression of key genes and signalling pathways involved in breast cancer progression and apoptosis.