miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics

Foteini Kouri, Carissa Ritner, Alexander H Stegh*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Glioblastoma (GBM) is an incurable cancer, with survival rates of just 14-16 months after diagnosis.1 Functional genomics have identified numerous genetic events involved in GBM development. One of these, the deregulation of microRNAs (miRNAs), has been attracting increasing attention due to the multiple biologic processes that individual miRNAs influence. Our group has been studying the role of miR-182 in GBM progression, therapy resistance, and its potential as GBM therapeutic. Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neurodevelopmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM. miR-182 sensitized glioma cells to TMZ-induced apoptosis, promoted glioma initiating cell (GIC) differentiation, and reduced tumor cell proliferation via knockdown of Bcl2L12, c-Met and HIF2A.2 To deliver miR-182 to intracranial gliomas, we have characterized Spherical Nucleic Acids covalently functionalized with miR-182 sequences (182-SNAs). Upon systemic administration, 182-SNAs crossed the blood-brain/bloodtumor barrier (BBB/BTB), reduced tumor burden, and increased animal subject survival.2-4 Thus, miR-182-based SNAs represent a tool for systemic delivery of miRNAs and a novel approach for the precision treatment of malignant brain cancers.

Original languageEnglish (US)
Pages (from-to)3794-3800
Number of pages7
JournalCell Cycle
Volume14
Issue number24
DOIs
StatePublished - Jan 1 2015

Fingerprint

Glioblastoma
MicroRNAs
temozolomide
Phenotype
Glioma
Therapeutics
Neoplasms
Atlases
Genomics
Tumor Burden
Blood-Brain Barrier
Brain Neoplasms
Nucleic Acids
Cell Differentiation
Survival Rate
Cell Proliferation
Genome
Apoptosis

Keywords

  • Glioblastoma
  • MiRNAs
  • Nanotechnology
  • Spherical nucleic acids (SNAs)

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

@article{d597eff9f57644ca88deeb8d40ad200f,
title = "miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics",
abstract = "Glioblastoma (GBM) is an incurable cancer, with survival rates of just 14-16 months after diagnosis.1 Functional genomics have identified numerous genetic events involved in GBM development. One of these, the deregulation of microRNAs (miRNAs), has been attracting increasing attention due to the multiple biologic processes that individual miRNAs influence. Our group has been studying the role of miR-182 in GBM progression, therapy resistance, and its potential as GBM therapeutic. Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neurodevelopmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM. miR-182 sensitized glioma cells to TMZ-induced apoptosis, promoted glioma initiating cell (GIC) differentiation, and reduced tumor cell proliferation via knockdown of Bcl2L12, c-Met and HIF2A.2 To deliver miR-182 to intracranial gliomas, we have characterized Spherical Nucleic Acids covalently functionalized with miR-182 sequences (182-SNAs). Upon systemic administration, 182-SNAs crossed the blood-brain/bloodtumor barrier (BBB/BTB), reduced tumor burden, and increased animal subject survival.2-4 Thus, miR-182-based SNAs represent a tool for systemic delivery of miRNAs and a novel approach for the precision treatment of malignant brain cancers.",
keywords = "Glioblastoma, MiRNAs, Nanotechnology, Spherical nucleic acids (SNAs)",
author = "Foteini Kouri and Carissa Ritner and Stegh, {Alexander H}",
year = "2015",
month = "1",
day = "1",
doi = "10.1080/15384101.2015.1093711",
language = "English (US)",
volume = "14",
pages = "3794--3800",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "24",

}

miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics. / Kouri, Foteini; Ritner, Carissa; Stegh, Alexander H.

In: Cell Cycle, Vol. 14, No. 24, 01.01.2015, p. 3794-3800.

Research output: Contribution to journalArticle

TY - JOUR

T1 - miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics

AU - Kouri, Foteini

AU - Ritner, Carissa

AU - Stegh, Alexander H

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Glioblastoma (GBM) is an incurable cancer, with survival rates of just 14-16 months after diagnosis.1 Functional genomics have identified numerous genetic events involved in GBM development. One of these, the deregulation of microRNAs (miRNAs), has been attracting increasing attention due to the multiple biologic processes that individual miRNAs influence. Our group has been studying the role of miR-182 in GBM progression, therapy resistance, and its potential as GBM therapeutic. Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neurodevelopmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM. miR-182 sensitized glioma cells to TMZ-induced apoptosis, promoted glioma initiating cell (GIC) differentiation, and reduced tumor cell proliferation via knockdown of Bcl2L12, c-Met and HIF2A.2 To deliver miR-182 to intracranial gliomas, we have characterized Spherical Nucleic Acids covalently functionalized with miR-182 sequences (182-SNAs). Upon systemic administration, 182-SNAs crossed the blood-brain/bloodtumor barrier (BBB/BTB), reduced tumor burden, and increased animal subject survival.2-4 Thus, miR-182-based SNAs represent a tool for systemic delivery of miRNAs and a novel approach for the precision treatment of malignant brain cancers.

AB - Glioblastoma (GBM) is an incurable cancer, with survival rates of just 14-16 months after diagnosis.1 Functional genomics have identified numerous genetic events involved in GBM development. One of these, the deregulation of microRNAs (miRNAs), has been attracting increasing attention due to the multiple biologic processes that individual miRNAs influence. Our group has been studying the role of miR-182 in GBM progression, therapy resistance, and its potential as GBM therapeutic. Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neurodevelopmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM. miR-182 sensitized glioma cells to TMZ-induced apoptosis, promoted glioma initiating cell (GIC) differentiation, and reduced tumor cell proliferation via knockdown of Bcl2L12, c-Met and HIF2A.2 To deliver miR-182 to intracranial gliomas, we have characterized Spherical Nucleic Acids covalently functionalized with miR-182 sequences (182-SNAs). Upon systemic administration, 182-SNAs crossed the blood-brain/bloodtumor barrier (BBB/BTB), reduced tumor burden, and increased animal subject survival.2-4 Thus, miR-182-based SNAs represent a tool for systemic delivery of miRNAs and a novel approach for the precision treatment of malignant brain cancers.

KW - Glioblastoma

KW - MiRNAs

KW - Nanotechnology

KW - Spherical nucleic acids (SNAs)

UR - http://www.scopus.com/inward/record.url?scp=84964033235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964033235&partnerID=8YFLogxK

U2 - 10.1080/15384101.2015.1093711

DO - 10.1080/15384101.2015.1093711

M3 - Article

C2 - 26506113

AN - SCOPUS:84964033235

VL - 14

SP - 3794

EP - 3800

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 24

ER -