Akademik Veri Yönetim Sistemi
56th Congress of the International Society of Paediatric Oncology (SIOP), Hawaii, Amerika Birleşik Devletleri, 17 - 20 Ekim 2024, cilt.71, sa.492, ss.492, (Özet Bildiri)
Background and Aims: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. NB is frequently observed in children under five years old and exhibits very heterogeneous clinical behavior. Treatment of the disease is based on risk stratification and dividing patients into low, intermediate, and high-risk groups. Current therapy modalities significantly improve the overall survival of NB patients, yet 5-year survival rates in patients in high-risk groups can reach a maximum of 60%. Inhibitory apoptosis protein (IAP) is overexpressed in many tumor types, including NB, and is associated with poor prognosis, aggressive phenotype, and advanced disease. A secondary mitochondrial caspase activator (SMAC) is released during the intrinsic apoptosis and inhibits IAPs. SMAC mimetics are agents developed on SMAC structure, and LCL-161 is one of them. The present study aimed to examine the effect of LCL-161 on transcriptomics changes. Methods: SH-SY5Y cells were treated with 50mM LCL-161 for 48 hours, and RNA isolation was performed with RNA isolation kit. RNA Sequencing was performed using a Nova Seq platform. Differential gene expressions were identified using pipeline in R programming, including Trimmomatic, HISAT2.2.1, and DESeq2 tools. Gene ontology analysis was performed to identify associated biological, molecular, and cellular pathways using g: Profiler and ShinyGo V0.75 tools. Gene expressions were studied with quantitative real-time PCR analysis (qPCR). Unpaired parametric T-test comparisons were performed using GraphPad Prism version 8.0.0 for Mac OS X. Results: LCL-161 treatment in SH-SY5Y cells resulted in upregulating the expression of 1595 genes and down-regulating the expression of 1382 genes. These genes were found to be related to endoplasmic reticulum (ER) stress pathways and related intrinsic apoptosis. qPCR analysis showed that LCL-161 treatment altered ER-stress-related gene expression in a dose and time-dependent manner. Conclusions: LCL-161 treatment increased ER-stress response in SH-SY5Y cells and contributed to apoptosis