Discovery of inhibitors of the HSP90-Calcineurin-NFAT pathway against glioblastoma

We report the application of mRNA sequencing technology for high-throughput profiling of genes expression changes in U87 glioblastoma cells after treatment with compound YZ129 that we identified in our screen. By analyzing the total mRNA sequencing between YZ129 treatment group and the DMSO control group, we identified that 181 genes were significantly downregulated (changed >2 folds), while 226 genes were significantly upregulated (changed >2 folds). The downregulated genes were mainly associated with hypoxia (ALDOC, TMEM45A, F3, FOS, GFBP1, etc), glycolysis (SLC2A1, ANGPTL4, ENO2, LDHA, PGM, PFKFB3, etc.), PI3K/AKT/mTOR pathway (AK4, SLC2A1, PDK1, PGM1, PLOD2, TUBA4A, etc.), EMT (epithelial-mesenchymal transition) (VEGFA, ID2, COL1A1, FOXC2, LOXL2, etc.), G2/M checkpoint (UBE2C, FBXO5 (Emi1), TOP2A, MCM5/6), etc. some of the upregualted genes may contribute to the possible chemoresistance, such as FOSB, INHBA, EDN1, IRS2, KDM6B. This study yields a global view on molecular response to YZ29 treatment in GBM cells at mRNA level. Examination of gene expression changes in U87 glioblastoma cells after treatment with drug YZ129 (versus DMSO control)