Cell type-specific Effect of miRZip-21 to Suppress miR-21 in Human Glioma Cell Lines

There are different subtypes of brain tumors, classified according to the origin of the abnormally proliferatedglial cells. Glioblastoma multiforma (GBM) is the grade 4 of brain tumors, gliomas, with the least life expectancy.microRNAs (miRNAs) are small, single stranded, non-coding RNAs with 20-25 nt length with post-transcriptional generegulatory activities. An altered expression of miRNAs is linked to developmental disorders and some diseases, mostimportantly cancers. miR-21 is a well-known microRNA, overexpressed in almost all cancer types, including braintumors. It targets several genes with vital roles in cellular pathways involve in proliferation, invasion and metastaticbehaviors. Exosomes are 30-100 nm extracellular vesicles which are packed with various molecules, includingmiRNAs. Here, we suppressed miR-21 expression level in HEK-293T cells by transfecting them with the miRZip-21vector. However, when U87-MG cells were cultured in the presence of exosomes isolated from conditioned medium ofengineered HEK-293T cells derived exosomes, we did not observe any suppressing effect on host cells’ miR-21expression level. Moreover, by analyzing the effects of miRZip-21-enriched cell’s conditioned media on three otherbrain cell lines including 1321N1, A-172 and DAOY, cell type-specific effects of exocrine miRZip-21 were revealed.These data suggested that cell lines from different brain tumor subtypes could exert different responses to microRNAbasedtherapies, based on their cellular origin and clinical behaviors.

Keywords:

miR-21 , Brain tumors , Glioblastoma multiforma , Exosomes