MicroRNA-dependent mechanisms underlying the function of a β-AMINO CARBONYL COMPOUND in glioblastoma cells.

Denis Mustafov, Shoib Siddiqui, Andreas Kukol, George Lambrou, Shagufta Waseem, Irshad Ahmad, Maria Braoudaki

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Glioblastoma multiforme (GBM) is an aggressive brain malignancy characterised by its invasive nature. Current treatment has limited effectiveness, resulting in poor patients’ prognoses. β-amino carbonyl (β-AC) compounds have gained attention due to their potential anti-cancerous properties. In vitro assays were performed to evaluate the effects of an in-house synthesised β-AC compound, named SHG-8, upon GBM cells. Small RNA-sequencing (sRNA-seq) and biocomputational analyses investigated the effects of SHG-8 upon the mirNome and its bioavailability within the human body. SHG-8 exhibited significant cytotoxicity in U87MG and U251MG GBM cells with IC50 values of 85μΜ and 100μΜ, respectively. Significant inhibition of cell migration and proliferation was induced in the presence of SHG-8. GBM cells treated with the compound were seen to release significant amounts of reactive oxygen species (ROS) at 50μΜ and 100μΜ SHG-8 concentrations. Annexin V staining also demonstrated that the compound led to apoptosis. sRNA-seq revealed a dramatic shift in miRNA expression profiles upon SHG-8 treatment and significant downregulation of miR-7974 and miR-21. Furthermore, miR-3648 was significantly upregulated in the presence of SHG-8. The sequencing analysis also identified that SHG-8 had a negative effect on the regulation of the Wnt/β-catenin pathway. Real-time polymerase chain reaction (RT-qPCR) demonstrated a significant downregulation of CORO1C, a target gene of miR-21. In silico analysis indicated SHG-8's favourable absorption, distribution, and potential to cross the blood-brain barrier. We concluded that SHG-8's inhibitory effects on GBM cells may involve miR-21-mediated CORO1C inhibition.
Original languageEnglish
JournalACS Omega
Publication statusAccepted/In press - 18 Jun 2024


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