Abstract 5931: Effect of necrosis on the migration, invasion and miRNA-mRNA association in glioblastoma cells

Abstract

Abstract Grade IV astrocytoma, also called glioblastoma multiforme (GBM), is considered the most malignant glial tumor. The purpose of our study is to understand the molecular mechanisms underlying the signaling network between necrotic tissues and GBM cells by exploring the effect of necrosis on GBM migration, invasion and miRNA-mRNA association. The migration and invasion of the CRT-MG human astroglioma cells were significantly enhanced by treatment with necrotic cells, as shown by assays for scratch wound healing and spheroid invasion. Incubation with necrotic cells induced IL-8 secretion in CRT-MG in dose-dependent manner. Immunohistochemical and immunoflurorescence analysis for IL-8 in human GBM tissues showed that positively stained cells were mainly distributed in perinecrotic region. Necrotic cells induced NF-κB and AP-1 activation and their DNA binding to IL-8 promoter, leading to enhanced IL-8 production and secretion in GBM cells. To determine the effect of necrosis on the miRNA profiles and regulatory relationship, the expression profiles of miRNA and mRNA and association between mRNA and their corresponding miRNAs were analyzed by next-generation sequencing (NGS). Our results demonstrate that necrotic cells enhance the migration and invasion of GBM cells through NF-κB/AP-1/IL-8 signaling pathway and induce dysregulation of miRNA and mRNA expression profiles in GBM cells. Citation Format: So-Hee Ahn, Hyunju Park, Jeong Seon Kim, Young-Ho Ahn, Sewha Kim, Min-Sun Cho, Jihee Lee Kang, Youn-Hee Choi. Effect of necrosis on the migration, invasion and miRNA-mRNA association in glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5931. doi:10.1158/1538-7445.AM2017-5931