Exploring the Role of microRNAs in Glioma Progression, Prognosis, and Therapeutic Strategies (original) (raw)
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Cellular & Molecular Biology Letters
Gliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secrete...
MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications
Journal of Cellular and Molecular Medicine, 2011
MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression. Dysregulation of these molecules has been indicated in the development of many cancers. Altered expression levels of several miRNAs were identified also in glioblastoma. It was repeatedly found that miRNAs are involved in important signalling pathways, which play roles in crucial cellular processes, such as proliferation, apoptosis, cell cycle regulation, invasion, angiogenesis and stem cell behaviour. Therefore, miRNAs represent promising therapeutic targets in glioblastoma. In this review, we summarize the current knowledge about miRNAs significance in glioblastoma, with special focus on their involvement in core signalling pathways, their roles in drug resistance and potential clinical implications.
MicroRNA Targeting as a Therapeutic Strategy Against Glioma
Current molecular medicine, 2013
Glioblastoma multiforme (GBM), the most common and aggressive form of primary brain tumor, presents a dismal prognosis. Current standard therapies are only able to improve patient survival by a few months. The search for alternative approaches in glioblastoma treatment, together with the recent discovery of a new class of small RNA molecules that are capable of regulating gene expression, prompted a race for a deeper and thorough understanding of how these molecules work. Today, it is known that microRNAs are involved in many cellular processes that are altered in GBM tumors, such as angiogenesis, invasion, cell proliferation and apoptosis. Research in this area is now gathering efforts to translate these findings into clinically relevant therapies that could improve the diagnosis and outcome of GBM patients. In this review, we discuss the use of microRNAs as potential diagnostic, prognostic and therapeutic tools against glioblastoma. We will also assess the current challenges and future perspectives of microRNA-based therapies, with a special focus on why this promising therapeutic approach is not yet into the clinic and how to overcome this limitation.
Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs
Neuro-Oncology, 2014
MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been found to play critical roles in most biological processes, including cancer. This is true for glioblastoma, the most common and lethal primary brain tumor, for which microRNAs have been shown to strongly influence cell viability, stem cell characteristics, invasiveness, angiogenesis, metabolism, and immune evasion. Developing microRNAs as prognostic markers or as therapeutic agents is showing increasing promise and has potential to reach the clinic in the next several years. This succinct review summarizes current progress and future directions in this exciting and steadily expanding field.
MicroRNA and Target Protein Patterns Reveal Physiopathological Features of Glioma Subtypes
PLoS ONE, 2011
Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.
Role of miRNa in glioma pathogenesis, diagnosis and therapeutic outcomes
Molecular Biology and Treatment Strategies for Gliomas [Working Title]
Glioma is the most aggressive tumor of glial cells of brain and spinal cord, even in the presence current multimodal therapeutic regimens the life expectancy of more then 2 year is very rare and it comprise 30 percent of all brain tumors. Micro RNAs (miRNAs) are short, non-coding RNAs produced naturally in the body and control gene expression. Many evidence-based hypotheses show that miRNA expression is aberrantly influenced in glioma due to amplification or deletion of miRNA genes, inappropriate transcriptional regulation of miRNAs, dysregulated epigenetic alterations, or faults in the miRNA biogenesis machinery. In some circumstances, miRNAs promote tumorigenesis, whereas under other circumstances, they can act as tumour suppressors in glioma. In glioma, miRNA involved in cell proliferation signalling, evasion of growth suppressors, resistance to cell death, tumour cell infiltration, metastasis, and angiogenesis. More and more research is pointing to miRNAs as prospective biomarke...
MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics
Cancer medicine, 2016
Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a...
Extensive modulation of a set of microRNAs in primary glioblastoma
Biochemical and Biophysical Research Communications, 2005
MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles in animals and plants by repressing translation or cleaving RNA transcripts. The specific modulation of several microRNAs has been recently associated to some forms of human cancer, suggesting that these short molecules may represent a new class of genes involved in oncogenesis. In our study, we examined by microarray the global expression levels of 245 microRNAs in glioblastoma multiforme, the most frequent and malignant of primary brain tumors. The analysis of both glioblastoma tissues and glioblastoma cell lines allowed us to identify a group of microRNAs whose expression is significantly altered in this tumor. The most interesting results came from miR-221, strongly upregulated in glioblastoma and from a set of brain-enriched miRNAs, miR-128, miR-181a, miR-181b, and miR-181c, which are down-regulated in glioblastoma.
MicroRNAs Regulate Cell Cycle and Cell Death Pathways in Glioblastoma
International Journal of Molecular Sciences, 2021
Glioblastoma (GBM), a grade IV brain tumor, is known for its heterogenicity and its resistance to the current treatment regimen. Over the last few decades, a significant amount of new molecular and genetic findings has been reported regarding factors contributing to GBM’s development into a lethal phenotype and its overall poor prognosis. MicroRNA (miRNAs) are small non-coding sequences of RNA that regulate and influence the expression of multiple genes. Many research findings have highlighted the importance of miRNAs in facilitating and controlling normal biological functions, including cell differentiation, proliferation, and apoptosis. Furthermore, miRNAs’ ability to initiate and promote cancer development, directly or indirectly, has been shown in many types of cancer. There is a clear association between alteration in miRNAs expression in GBM’s ability to escape apoptosis, proliferation, and resistance to treatment. Further, miRNAs regulate the already altered pathways in GBM, ...