DRES-15. GSK3 BETA AND hnRNPA1 (RNA BINDING PROTEIN) COOPERATES WITH cMyc TRANSCRIPTIONAL REGULATOR, ANTAGONIZES GSK3 ALPHA UNDER THERAPEUTIC STRESS. (5th November 2018)

• Record Type: Journal Article
• Authors: Yadav, Ajay; Vashistha, Vidhi
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi78
• Page End: vi78
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.322
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Oncogenic cooperation activity tends these glioma cells to acquire drug resistance. Where GSK3 beta isoform cooperates cMyc antagonizes GSK3 alpha isoform. Down regulated expression of GSK3 alpha cooperates elevated hnRNPA1 expression, evolving glioma development. Occurrence of hnRNPA1 dependent alternative oncogenic variant is one of the resistance mechanism. Inhibiting GSK3 beta isoform using specific siRNAs is one the approach rather than to inhibit GSK3 kinase activity, also downregulate hnRNPA1 which is cMyc dependent. Using Chromatin Immuniprecipitation approach we observed potential differences in between transcriprional regulators of GSK3 beta and GSK3 alpha isoform. Positive feedback mechanism of alpha and beta isorform of GSK3 to stabilize cMyc, therefore inhibiting expression of heterogenous ribonucleor protein family members. Interfering the positive feed back GSK3 beta- cMyc-GSK3 beta, is major hallmark to catch on cMyc transcriptional regulator. In another experiment inhibition of PI3 kinase/ AKT pathway using specific inhibitors elevates GSK3 beta and hnRNPA1 but not GSK3 alpha, associates with cMyc, indicating potential role of GSK3 beta isoform in glioma resistance development. Immunohistochemistry based analysis shows inverse correlation between GSK3 alpha and hnRNPA1.