Circulating miRNAs are emerging as an interesting research area, because of their potential role as novel biomarkers and therapeutic targets.
Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs downregulation is a hallmark of malignant transformation.
MicroRNAs (miRNAs), one kind of post-transcriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes,
Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.
miRNAs regulate gene expression in a sequence-specific fashion; miRNAs bind to 3′untranslated regions (UTRs) of mRNAs and then affect the translation and/or stability of that mRNA, leading to a reduction in protein levels.
The abnormal levels of miRNAs in tumors have important pathogenetic consequences.
Some miRNAs are over-expressed in tumors and act as oncogenes, promoting tumor aggravation by down-regulating tumor suppressors.
Aberrant miRNA expression has been observed in human glioblastoma (GBM).
Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis.
Among noncoding RNAs, microRNAs (miRNAs) have been most extensively studied, and their biology has repeatedly been proven critical for central nervous system pathological conditions.
Circulating microRNAs (miRNAs) are a new class of highly promising cancer biomarkers.
Deregulation of microRNAs (miRNAs) expression has been associated with cancer formation through alterations in gene targets.
MicroRNA (miRNA) contributes to the pathogenesis of various types of tumor, including glioblastoma (GBM). So far, miRNA has been shown to function in regulating protein-coding gene expression. This allows miRNAs to have direct function in regulation of various cellular events, including cell proliferation, apoptosis, and differentiation. Great progress has been made in identifying novel tumor-related miRNAs and their potential target genes 3).
miRNA may play a critical role during progression from low grade gliomas to anaplastic gliomas or secondary glioblastomas and not contribute to the malignant progression from anaplastic gliomas to secondary glioblastomas 4).
Wnt/β-catenin signaling pathway is frequently dysregulated in human tumors and plays a critical role in tumorigenesis; however, the roles of microRNAs in mediating Wnt/β-catenin pathway are not well understood.
As the involvement of miRNAs in the carcinogenesis is well known, Ivo D'Urso et al carried out a pilot study to identify, as potential biomarkers, differentially expressed microRNAs in blood samples of patients affected by glioma. We studied the miRNAs' expression, by means of microarray and Real-Time PCR, in 30 blood samples from glioma patients and in 82 blood samples of patients suffering from: (a) various neurological disorders (n=30), (b) primary B-lymphoma of the Central Nervous System (PCNSL, n=36) and © secondary brain metastases (n=16). By quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR), we identified significantly increased levels of two candidate biomarkers, miR-15b and miR 21, in blood of patients affected by gliomas. ROC analysis of miR-15b biomarker levels allowed to differentiate patients with tumour from patients without glioma. Furthermore, combined expression analyses of miR15b and miR-21 distinguished between patients with and without glioma (90% sensitivity and 100% specificity). In addition, a decrement in the expression levels of miR-16 characterized glioblastomas compared to low grade and anaplastic gliomas. In conclusion, this pilot study suggest that it's possible to identify the disease state by meaning miR-15b and miR-21 markers in blood, while miR-16 can be used to distinguish glioblastoma from other grade gliomas. They can potentially be used as biomarkers for non-invasive diagnosis of gliomas; further studies are mandatory to confirm our preliminary findings 5).
miR 613 …..
Jiang et al., found a positive correlation between the levels of miR-127-3p and the cell migration and invasion abilities in several human GBM cell lines. Theyshowed that miR-127-3p promoted cell migration and invasion of GBM cells using in vitro cell lines and in vivo mouse models. They identified SEPT7, a known tumor-suppressor gene that has been reported to suppress GBM cell migration and invasion, as a direct target of miR-127-3p. SEPT7 was able to partially abrogate the effect of miR-127-3p on cell migration and invasion. In addition, microarray analysis revealed that miR-127-3p regulated a number of migration and invasion-related genes. Finally, they verified that miR-127-3p affected the remodeling of the actin cytoskeleton mediated by SEPT7 in GBM cells 6).
MiR-132, miR-15a and miR-16 have been implicated in the pathogenesis of many types of cancer, including pituitary tumors. However, the molecular mechanism of these miRNAs in pituitary tumor growth and metastasis is still unclear. Here, we showed that miR-132 and miR-15a/16 were less expressed in pituitary tumor cell lines, as well as in invasive pituitary tumor tissues, compared to non-invasive tumor tissues. We described that overexpression of miR-132 and miR-15a/16 resulted in the suppression of pituitary tumor cell proliferation, migration and invasion, respectively, and also inhibits the expression of proteins involved in Epithelial to Mesenchymal Transition (EMT). Then, we show that these miRNAs synergistically target Sox5 in pituitary tumor. Moreover, we found that Sox5 overexpression partially rescued miR-132, miR-15a and miR-16-mediated inhibition of cell migration, invasion and cell growth. Finally, we confirmed that Sox5 was upregulated in invasive pituitary tumor tissues, compared to non-invasion tissues. In conclusion, our data indicate that miR-132 and miR-15a/16 act as tumor suppressor genes in pituitary tumor by directly targetting Sox5, and imply that these miRNAs have potential as therapeutic targets for invasive pituitary tumor 7).
Results support that dysregulated microRNAs may have a pathogenic role in intracranial aneurysms. Disruption of the protein translation process may have a pathogenic role in the development of intracranial aneurysms 8).
The molecular mechanisms behind intracranial aneurysm formation and rupture remain poorly understood.
The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled.
A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets.
Overall, 7 unruptured intracranial aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143-5p (fold change -11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms.
This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed 9).
A total of 50 microRNAs were found to be differentially expressed in mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) compared with healthy controls. Among them, 2 were increased and 48 were decreased. The 6 significant differentially expressed candidate microRNAs (miR-3613-5p, miR-4668-5p, miR-8071, miR-197-5p, miR-4322, and miR-6781-5p ) in exosome were validated. The bioinformatics analysis showed that the potential target genes of these microRNAs were involved in biological processes, molecular functions, and cellular components. Similarly, these microRNAs also affected axon guidance, pathways in cancer, regulation of the actin cytoskeleton, focal adhesion, the calcium signaling pathway, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Among 6 candidate microRNAs, miR-8071 had the best diagnostic value for mTLE-HS with 83.33% sensitivity and 96.67% specificity, and was associated with seizure severity. This study indicated that exosomal microRNAs, may be regulators for the seizure development in mTLE-HS, and can be used as potential therapeutic targets and biomarker for diagnosis in mTLE-HS 10).