Abstract
microRNAs (miRNAs) are no longer deemed small pieces of RNA "trash" in the human transcriptome but are considered to be master regulators of gene expression that are critical in maintaining cellular homeostasis post-transcriptionally. The concept triggers great interest in studying miRNA dysregulations in human diseases, especially in cancers. Glioblastoma (GBM) has long been the leading cause of the high mortality and morbidity of CNS tumors in adults, which is a consequence of the lack of strategies to reverse the hallmark features of GBM (e.g., borderless expansion and diffuse infiltration). In the past decade, dissecting the molecular architecture of GBM has led to a better understanding of the molecular basis of the hallmarks, generating many promising pharmacological protein targets. However, few clinical responses have been highlighted, suggesting the demand for new therapeutic strategies and targets. In this review, we systemically summarize the context-dependently validated miRNAs with one or more functional targets in the development of GBM hallmarks and review the current miRNA-targeting strategies. We note that only a few miRNA-based therapeutics are trialed for clinical significance, and none of them is tailored to GBM, thereby urging us to bring miRNA therapeutics to the front line either alone or in combination.
Highlights
Glioblastoma (GBM), the WHO grade IV tumor of the CNS, is the most prevalent and aggressive glioma variant in adults [1]
Gross total surgical excision followed by involved-field radiotherapy up to a total dose of 60 Gy was the only accepted GBM management by physicians for decades, as no chemotherapeutic agents significantly improved the survival of GBM patients until the introduction of temozolomide, an oral alkylating agent
Following the export of pre-miRNA from the nucleus, Dicer, a cytoplasmic RNase III that commonly forms a complex with TAR RNA binding protein (TRBP), binds to the pre-miRNA and further processes the hairpin miRNA precursors into approximately 22 nt miRNA duplexes [4]
Summary
Glioblastoma (GBM), the WHO grade IV tumor of the CNS, is the most prevalent and aggressive glioma variant in adults [1]. As our knowledge of the transcriptome space has expanded, several other RNA species, including large intergenic non-coding RNAs (lincRNAs) [11,12,13], transcribed ultraconseverved regions (T-UCRs) [14], pseudogenes [15,16,17] and circular RNAs (circRNAs) [18, 19], may serve as ceRNAs, functioning in trans to regulate levels of free miRNAs and other RNAs. compared with the cis regulatory networks, ceRNA research is obviously in its infancy, and more compelling evidence is still required to ascertain whether ceRNA crosstalk represents a widespread network of RNA regulation. It has been documented that miRNA dysregulation could play important roles in GBM development and progression
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