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dc.contributor.authorMunoz, Jessian L.en_US
dc.contributor.authorRodriguez-Cruz, Vivianen_US
dc.contributor.authorRamkissoon, Shakti H.en_US
dc.contributor.authorLigon, Keith L.en_US
dc.contributor.authorGreco, Steven J.en_US
dc.contributor.authorRameshwar, Pranelaen_US
dc.date.accessioned2015-04-01T15:30:15Z
dc.date.issued2015en_US
dc.identifier.citationMunoz, Jessian L., Vivian Rodriguez-Cruz, Shakti H. Ramkissoon, Keith L. Ligon, Steven J. Greco, and Pranela Rameshwar. 2015. “Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level.” Oncotarget 6 (2): 1190-1201.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14351259
dc.description.abstractGlioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ-resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR, reporter gene studies, western blots, target protector oligos and ectopic expression identified miR-9 as the target of PTCH1 in resistant GBM cells with concomitant activation of SHH signaling. MiR-9 mediated increases in the drug efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM patients and in an early passage GBM cell line from a patient with recurrent GBM but not from a naïve patient. Pharmacological inhibition of SHH signaling sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells by a SHH-independent method in GBM cells for TMZ resistance. The identified pathways could lead to new strategies to target GBM with combinations of drugs.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359226/pdf/en
dash.licenseLAAen_US
dc.subjectglioblastomaen
dc.subjectMicroRNA-9en
dc.subjectPTCHen
dc.subjectTemozolomideen
dc.subjectP-gpen
dc.titleTemozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog levelen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorRamkissoon, Shakti H.en_US
dc.date.available2015-04-01T15:30:15Z
dc.identifier.doi10.18632/oncotarget.2778
dash.contributor.affiliatedRamkissoon, Shakti H.
dash.contributor.affiliatedLigon, Keith


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