Abstract

Glioblastoma multiforme (GBM) is the most common and most aggressive human brain tumor. However, despite decades of basic science and clinical research, there is no quick, widely used prognostic criterion for GBM patients (except for non-molecular parameters, such as age; lower survival is correlated with older age) and the outcome for GBM patients remains dismal, with an average survival duration of only 15 months. Thus, new innovative, mechanism-based approaches are necessary for the management of patients with GBM. We have discovered a new regulatory axis based on a novel miR-21-Sox2 axis in GBM patients and patient glioblastoma-derived stem cells through bioinformatic and biochemical studies. This axis appears to classify GBM patients into distinct classes. Based on these results, here we propose to prove or disprove the novel central hypothesis that our GBM classification based on the miR-21-Sox2 axis can produce new prognostic approaches for GBM patients and that this mechanism can also be utilized to develop more effective, less toxic personalized treatment regimens for GBM patient care

Public Health Relevance

The mean survival duration of patients with glioblastoma multiforme (GBM), the most common form of glioma, is approximately 15 months and there is no effective therapy. If the Specific Aims of this grant application are completed, not only we wil have the understanding of a new mechanistic axis of GBM tumorigenesis, but this information will also have potentially novel and unconventional translational impact in terms of detection, predict patient outcome and design more effective therapeutic approaches than what is currently used.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS081684-04
Application #
8851696
Study Section
Basic Mechanisms of Cancer Therapeutics Study Section (BMCT)
Program Officer
Fountain, Jane W
Project Start
2012-09-01
Project End
2016-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
4
Fiscal Year
2015
Total Cost
$379,227
Indirect Cost
$139,210

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Marisetty, Anantha L; Singh, Sanjay K; Nguyen, Tran N et al. (2017) REST represses miR-124 and miR-203 to regulate distinct oncogenic properties of glioblastoma stem cells. Neuro Oncol 19:514-523
Singh, Sanjay K; Marisetty, Anantha; Sathyan, Pratheesh et al. (2015) REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells. Stem Cell Res 15:305-11
Sathyan, Pratheesh; Zinn, Pascal O; Marisetty, Anantha L et al. (2015) Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact. J Neurosci 35:15097-112