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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Targeting strategies on miRNA-21 and PDCD4 for glioblastoma
Gang Wang1, Jun Jie Wang2, Hong Ming Tang3
1Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai 200235, China; Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200000, China.
Abstract:
MicroRNAs (miRNAs) are often deregulated in glioblastoma multiforme (GBM). Downregulation of microRNA-21 (miR-21), especially in GBM, is responsible for increased apoptosis, decreased cell proliferation and invasion, increased G0/G1 cell cycle arrest, and reduced chemotherapeutic resistance to doxorubicin. Furthermore, it is a critical regulator of multiple downstream genes and signaling pathways involved in gliomagenesis. Programmed cell death 4 (PDCD4) is critical in mediating apoptosis in GBM, and is downregulated by miR-21, which may mediate the resistance of glioblastoma cells against chemotherapy or radiation via its target genes PDCD4. Evidence is mounting that how alterations of these miRNAs transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the roles of miRNAs family members (particularly miR-21 and its target gene PDCD4) in tumors like glioblastoma and new targeting strategies, as examples some new targeting therapeutic methods and molecular mechanisms of signal pathways in glioblastoma therapeutics, to give the reader the current trends of approach to target regulation of these miRNA and genes for future glioma therapies.
Insights
MicroRNA-21 (miR-21) downregulation in glioblastoma (GBM) impacts apoptosis, proliferation, and chemoresistance. Targeting miR-21 and its gene PDCD4 offers new therapeutic strategies for glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators frequently deregulated in glioblastoma multiforme (GBM).
- miR-21 downregulation in GBM correlates with increased apoptosis, decreased proliferation and invasion, and reduced doxorubicin resistance.
- miR-21 targets multiple genes and signaling pathways implicated in gliomagenesis, including Programmed Cell Death 4 (PDCD4).
Purpose of the Study:
- To review the role of miR-21 and its target PDCD4 in glioblastoma development and progression.
- To explore novel therapeutic strategies targeting miRNA and gene regulation in glioma.
Main Methods:
- Literature review focusing on the molecular mechanisms of miR-21 and PDCD4 in glioblastoma.
- Analysis of current and emerging therapeutic approaches targeting miRNA and associated signaling pathways.
Main Results:
- miR-21 downregulation is linked to glioblastoma aggressiveness and chemoresistance, partly via PDCD4.
- Alterations in miRNA transcription factors contribute to tumor initiation, maintenance, and progression.
- Targeting miR-21 and PDCD4 presents a promising avenue for glioblastoma treatment.
Conclusions:
- miR-21 and PDCD4 are critical players in glioblastoma pathogenesis and therapeutic resistance.
- Understanding these molecular interactions is key to developing effective future glioma therapies.
- Novel strategies focusing on miRNA regulation offer new hope for glioblastoma treatment.
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