High-grade gliomas (HGGs) are malignant primary brain tumors of glial cell origin. Despite optimal course of treatment, including maximal surgical resection followed by adjuvant chemo- and/or radiotherapy, the prognosis still remains poor. The main reason is the commonly occurring chemo- and radioresistance of these tumors. In recent years, several signaling pathways, especially PI3K/AKT and ATM/CHK2/p53, have been linked to the resistance of gliomas. Moreover, additional studies have shown that these pathways are significantly regulated by microRNAs (miRNAs), short endogenous RNA molecules that modulate gene expression and control many biological processes including apoptosis, proliferation, cell cycle, invasivity, and angiogenesis. MiRNAs are not only highly deregulated in gliomas, their expression signatures have also been shown to predict prognosis and therapy response. Therefore, they present promising biomarkers and therapeutic targets that might overcome the resistance to treatment and improve prognosis of glioma patients. In this review, we summarize the current knowledge of the functional role of miRNAs in gliomas resistance to chemo- and radiotherapy.

• MeSH
• Apoptosis MeSH
• Ataxia Telangiectasia Mutated Proteins MeSH
• Checkpoint Kinase 2 MeSH
• Drug Resistance, Neoplasm genetics   MeSH
• DNA-Binding Proteins metabolism   MeSH
• Phosphatidylinositol 3-Kinases metabolism   MeSH
• Glioma * drug therapy   genetics   radiotherapy   MeSH
• Neoplasm Invasiveness MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Tumor Suppressor Proteins metabolism   MeSH
• Tumor Suppressor Protein p53 metabolism   MeSH
• Brain Neoplasms drug therapy   genetics   radiotherapy   MeSH
• Protein Serine-Threonine Kinases metabolism   MeSH
• Cell Cycle Proteins metabolism   MeSH
• Proto-Oncogene Proteins c-akt metabolism   MeSH
• Radiation Tolerance genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• ATM protein, human MeSH Browser
• Ataxia Telangiectasia Mutated Proteins MeSH
• Checkpoint Kinase 2 MeSH
• CHEK2 protein, human MeSH Browser
• DNA-Binding Proteins MeSH
• MicroRNAs MeSH
• Tumor Suppressor Proteins MeSH
• Tumor Suppressor Protein p53 MeSH
• Protein Serine-Threonine Kinases MeSH
• Cell Cycle Proteins MeSH
• Proto-Oncogene Proteins c-akt MeSH
• TP53 protein, human MeSH Browser

For the many years, the central dogma of molecular biology has been that RNA functions mainly as an informational intermediate between a DNA sequence and its encoded protein. But one of the great surprises of modern biology was the discovery that protein-coding genes represent less than 2% of the total genome sequence, and subsequently the fact that at least 90% of the human genome is actively transcribed. Thus, the human transcriptome was found to be more complex than a collection of protein-coding genes and their splice variants. Although initially argued to be spurious transcriptional noise or accumulated evolutionary debris arising from the early assembly of genes and/or the insertion of mobile genetic elements, recent evidence suggests that the non-coding RNAs (ncRNAs) may play major biological roles in cellular development, physiology and pathologies. NcRNAs could be grouped into two major classes based on the transcript size; small ncRNAs and long ncRNAs. Each of these classes can be further divided, whereas novel subclasses are still being discovered and characterized. Although, in the last years, small ncRNAs called microRNAs were studied most frequently with more than ten thousand hits at PubMed database, recently, evidence has begun to accumulate describing the molecular mechanisms by which a wide range of novel RNA species function, providing insight into their functional roles in cellular biology and in human disease. In this review, we summarize newly discovered classes of ncRNAs, and highlight their functioning in cancer biology and potential usage as biomarkers or therapeutic targets.

• MeSH
• Humans MeSH
• Neoplasms genetics   MeSH
• RNA, Untranslated genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• RNA, Untranslated MeSH

MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression. Single nucleotide polymorphisms (SNPs) may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. Specific SNPs were identified in predicted miRNA target sites within 3' untranslated regions of mRNAs. These SNPs have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. Resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to cancer and its onset as well as for estimates of prognosis and therapy response. In this review, we provide a comprehensive list of potentially functional miRNA-related SNPs and summarize their importance as candidate cancer biomarkers.

• MeSH
• 3' Untranslated Regions MeSH
• Genetic Predisposition to Disease MeSH
• Genotype MeSH
• Polymorphism, Single Nucleotide * MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Molecular Epidemiology methods   MeSH
• Neoplasms genetics   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• 3' Untranslated Regions MeSH
• MicroRNAs MeSH

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery.

• MeSH
• DNA Modification Methylases genetics   metabolism   MeSH
• Adult MeSH
• DNA Repair Enzymes genetics   metabolism   MeSH
• Glioblastoma diagnosis   genetics   metabolism   mortality   MeSH
• Kaplan-Meier Estimate MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Methylation MeSH
• MicroRNAs biosynthesis   MeSH
• Biomarkers, Tumor genetics   metabolism   MeSH
• Tumor Suppressor Proteins genetics   metabolism   MeSH
• Brain Neoplasms diagnosis   genetics   metabolism   mortality   MeSH
• Disease-Free Survival MeSH
• Prognosis MeSH
• Promoter Regions, Genetic * MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA Modification Methylases MeSH
• DNA Repair Enzymes MeSH
• MGMT protein, human MeSH Browser
• MicroRNAs MeSH
• MIrn181 microRNA, human MeSH Browser
• MIRN195 microRNA, human MeSH Browser
• MIRN196 microRNA, human MeSH Browser
• MIRN21 microRNA, human MeSH Browser
• Biomarkers, Tumor MeSH
• Tumor Suppressor Proteins MeSH

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.

• MeSH
• Down-Regulation MeSH
• Glioblastoma genetics   pathology   MeSH
• Humans MeSH
• MicroRNAs genetics   MeSH
• Models, Genetic MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Signal Transduction genetics   MeSH
• Up-Regulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• MicroRNAs MeSH
• MIRN197 microRNA, human MeSH Browser
• MIRN21 microRNA, human MeSH Browser