BIOL-09. HNRNPA1 SPLICED VARIANT: KEY RESISTANT GENE SIGNATURE IN GLIOMAS

Abstract

Glioblastoma is inevitably a recurrent cancer. Despite of recent advancement, temozolomide remain the prescribed lifeline drug, after the surgery. Inadvertently, MGMT (O6-methylguanine-DNA-methyltransferase) expression mechanistically linked with Temozolomide (alkylating drug) glioma resistant development. To understand the resistant against Temozolomide sought to deciphered, by making invitro drug resistant glioma cell lines. RNA seq analysis over a illumina platform; drug resistant glioma cell lines showed various critical key factor such as splice factor hnRNPA1 and deubiquitinating enzymes were showed to highly upregulated in resistant cell lines. Commonly, from our previous study, the stability of hnRNPA1 in presence of USP5 were showed to promote cell survival, whereas knocking down of USP5 significantly lower down the telomerase activity and NAD/NADH ratio enlarge. Furthermore, expression of MGMT was showed significantly downregulated in hnRNPA1 knock down T98G glioma cells, as well as in U87 Temozolomide resistant cells. Extrinsic apoptosis pathway was showed more prevalent in hnRNPA1 knock down glioma cells in presence of Trail ligand. Interestingly, we found one more spliced variants of hnRNPA1 exclusively expressing in drug resistant cells is new finding. Selectively knocking down of hnRNPA1 splice variant promotes apoptosis. RNA seq analysis followed the comparison between two hnRNPA1 spliced variant knock down, drug resistant glioma cell lines showed differentially expressed transcript support our finding to be distinctly regulated by hnRNPA1 spliced variants. Spliced variant of hnRNPA1 showed a potential therapeutic candidate signature.