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MO_7_2638 - Time sequential changes of epithelial-mesenchymal transition signaling induced by ionizing radiation using next-generation sequencing in glioblastoma

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Time sequential changes of epithelial-mesenchymal transition signaling induced by ionizing radiation using next-generation sequencing in glioblastoma
Y. J. Kim1, J. H. Kim2, K. Kim1, I. H. Kim2, and S. Y. Seo1; 1Seoul National University Hospital, Seoul, Korea, Republic of (South), 2Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea, Republic of (South)

Purpose/Objective(s): Epithelial-mesenchymal transition (EMT) is considered as one of the mechanisms of treatment resistance in glioblastoma. We evaluated a time sequential changes of EMT signaling in glioblastoma induced by ionizing radiation.

Materials/Methods: The cell line U-373 MG (human glioblastoma) was irradiated with 6Gy of high energy X-ray (6MV) with dose rate of 6 Gy/min. Next generation sequencing (NGS) was performed on the cell line before irradiation (baseline), 6 hours, 24 hours, and 48 hours after irradiation and database of essential genes (DEG) was evaluated in each period. The DEGs were compared with those included in the 128 of the GeneSets. P value from the Fisher exact test and Q value from the Benjamini Hochberg methods were calculated. All KEGG map pathways were evaluated and the EMT related KEGG pathways were assessed using the EMT gene database (dbEMT).

Results: GeneSet analysis showed that ionizing radiation up-regulated the expression of the GeneSet of the wholemark of EMT at 6 hours and 24 hours after irradiation. On KEGG pathway analysis, extracellular matrix (ECM) receptor interactions increased over time and the expression of miRNA-21 increased at 6, 24, and 48 hours after irradiation resulting in cell growth and survival pathway. Increased RTK expression suggested RTK-induced EMT process. HIF-α induced hypoxia and activated TGF-β signaling pathway, which is related with EMT. TGF- β activated Smad2/3 followed by activation of Smad4.

Conclusion: Ionizing radiation may promote EMT in glioblastoma, resulting in treatment related resistance. miRNA-21 may play a critical role in EMT after irradiation. EMT blocking to prevent treatment resistance may be a promising strategy to increase survival in glioblastoma.

Author Disclosure: Y. Kim: None.

Yi-Jun Kim, MD

Biography:
I worked as a resident and fellow at the Department of Radiation Oncology at Ewha Womans University Hospital and Seoul National University Hospital (SNUH). Currently, I am a research professor at the Center for Precision Medicine of SNUH after completing the course of Certified Pyhsician in BioMedical Informatics (CPBMI) at SNUH.

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