Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 181, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.addr.2021.114082
Keywords
Posttranscriptional regulation; GBM; Adenine- and Uridine-rich elements; Cytoplasmic translocation; HuR multimerization; Small molecule inhibitors
Categories
Funding
- NIH [R01NS092651, R21NS111275-01]
- Dept. of Veterans Affairs [BX001148, R01 CA200624]
- O'Neal Neuro-oncology Research Acceleration Fund
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Glioblastoma (GBM) is a malignant brain tumor characterized by treatment resistance due to cellular and molecular heterogeneity. Targeting HuR, a regulator of posttranscriptional RNA regulation, represents a plausible therapeutic strategy for attacking GBM.
Glioblastoma (GBM) is a malignant and aggressive brain tumor with a median survival of -15 months. Resistance to treatment arises from the extensive cellular and molecular heterogeneity in the three major components: glioma tumor cells, glioma stem cells, and tumor-associated microglia and macrophages. Within this triad, there is a complex network of intrinsic and secreted factors that promote classic hallmarks of cancer, including angiogenesis, resistance to cell death, proliferation, and immune evasion. A regulatory node connecting these diverse pathways is at the posttranscriptional level as mRNAs encoding many of the key drivers contain adenine- and uridine rich elements (ARE) in the 30 untranslated region. Human antigen R (HuR) binds to ARE-bearing mRNAs and is a major positive regulator at this level. This review focuses on basic concepts of ARE-mediated RNA regulation and how targeting HuR with small molecule inhibitors represents a plausible strategy for a multi-pronged therapeutic attack on GBM.(c) 2021 Published by Elsevier B.V.
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