scholarly journals The role of miRNA in selected tumors development: Potential use in diagnostics

2021 ◽  
Vol 75 ◽  
pp. 1-11
Author(s):  
Patrycja Paciorek ◽  
Mariusz Żuberek ◽  
Agnieszka Grzelak
Keyword(s):  
Gene Expression ◽  
Mirna Expression ◽  
Regulation Of Gene Expression ◽  
Regulatory Function ◽  
Cancer Information ◽  
Bodily Fluids ◽  
Experimental Therapies ◽  
Oncological Diagnostics ◽  
Potential Use

MicroRNAs (miRNAs) are small ribonucleic acid molecules that, although not translated, perform an important regulatory function in eukaryotic cells. Their physiological function is to maintain cell homeostasis. Impaired miRNA expression can cause the development of many diseases including cancer. MiRNA biological activity is based on inhibiting the formation of proteins, including oncogenic and anti-oncogenic proteins. Mutations at the coding sites for such miRNAs can lead to overproduction or reduction of the production of the above-mentioned proteins. The discovery of miRNAs and understanding their role in the cell opened new ways for diagnosing cancer. Therefore, changes in the level of relevant miRNAs in the bloodstream or other bodily fluids can be a diagnostic marker of disease. Oncological diagnostics could be based on examining the patient’s miRNA profile and comparing it with previously developed profiles of miRNAs changes associated with the occurrence of a given type of cancer. Information on changes in miRNA profiles that are key to regulating gene expression associated with tumorigenic processes could contribute to the development of experimental therapies based on restoring the original level of miRNA in cells and thereby restoring normal regulation of gene expression. New methods of silencing and enabling miRNA expression may, in the future, result in effective therapeutic solutions.

scholarly journals The Role of microRNAs in the Pathogenesis of Erdheim-Chester Disease and Their Potential Use As Biomarkers for Diagnosis and Prognosis of the Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2397-2397
Author(s):  
Ran Weissman ◽  
Nir Pilar ◽  
Benjamin H Durham ◽  
Michelle Ki ◽  
Roei D Mazor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Mirna Expression ◽  
Target Genes ◽  
Differentially Expressed ◽  
Mirna Expression Pattern ◽  
Differentially Expressed Mirnas ◽  
Potential Use ◽  
Novel Therapeutic

Abstract Background: Erdheim-Chester disease (ECD) is a rare hematological malignancy, belonging to the L-group histiocytoses. ECD is characterized by multi-systemic proliferations of mature histiocytes in a background of inflammatory stroma. The inflammatory and neoplastic characteristics of the disease comprise a complex medical challenge for its diagnosis and treatment. MicroRNAs (miRNAs/miRs) are short non-coding RNAs (~22 nucleotides) that regulate gene expression in a sequence specific manner and play an important role in cancer development and progression. Since miRNAs are released into the blood by tumor cells, they may be used as biomarkers to distinguish between cancer patients and healthy individuals and to assist in determining treatment response. Moreover, miRNA-mRNA interactions can determine the molecular mechanism by which miRNAs and their target genes are involved in ECD and may suggest novel therapeutic options for these patients. To date, this is the first study elucidating the role of miRNA in ECD. Aims: The main focus of this study is to identify miRNAs that are differentially expressed in ECD patients compared to healthy controls and any clinical utility they have as potential biomarkers in ECD diagnosis, as well as to investigate their role in ECD pathogenesis, which may lead to new therapeutic options. Preliminary results: Using the nCounter Human miRNA Expression Assay (NanoString Technologies), we analyzed the plasma miRNA expression profiles of 6 ECD patients (BRAF V600E) compared to 6 healthy individuals. Of the 800 mature miRNAs analyzed, 234 miRNAs showed different expression levels in these samples. Principal component analysis (PCA) was applied to experimental quality control. The miRNAs from healthy donors were clustered separately from the ECD samples indicating a distinct miRNA expression pattern between these groups (Fig. 1A, 1B). Among the 131 miRNAs remaining in the final analysis (FDR<0.05),110 miRNAs were downregulated in ECD patients compared to those of healthy controls, and 21 miRNAs were upregulated in ECD samples compared to those of the controls. We validated the analysis method by quantitative real-time polymerase chain reaction (qRT-PCR) and found a positive correlation between miRs-15a, 16, 125a, 223, 21, 34a, 155 and miR-630 expression obtained by the NanoString array. This may indicate the potential use of miRNAs as biomarkers in ECD. To determine potential target genes and signaling pathways implicated in ECD, we analyzed the predicted pathways of the top 30 downregulated miRNAs that were differentially expressed between the two groups using the Ingenuity® Pathway Analysis (IPA) and DIANA-miRPath v3.0 database. Reassuringly, the analysis identified cancer, inflammatory disease, and inflammatory response (p<0.01) as the main disease and disorder related with the miRNA expression pattern, as well as oncogenic pathways such as MAPK, PI3K-AKT, RAS, ErbB, Hippo, and mTOR as the main molecular pathways related to the differentially-expressed miRNAs (p<0.009). This finding suggests that low expression of miRNAs results in up regulation of target genes that participate in cell survival signaling. These augmented pathways may be inhibited by novel therapeutic treatments such as PI3K inhibitors, mTOR pathway inhibitors, and MEK inhibitors in ECD patients. Next, we examined if there is any correlation between the predicted target genes of the miRNAs (obtained by IPA) and the experimentally validated gene expression pattern in ECD patients. To that end, we downloaded RNA-seq results of ECD patients from the GEO database (GSE74442 deposited by Diamond et al) and compared this list to our predicted miRNA targets in ECD patients, using Gene Set Enrichment Analysis (GSEA). We found a positive correlation between the gene expression reported in the literature and the predicted target of our deregulated miRNAs (Fig. 2), indicating that the predicted target genes are enriched in this data set, suggesting that the differentially expressed miRNAs might have a crucial role in the pathogenesis of ECD. Conclusions: Our preliminary data highlight the unique inflammatory and neoplastic features characteristic of ECD. These deregulated miRNAs may highlight new candidate gene targets allowing for a better understanding of the molecular mechanisms underlying the development of ECD and propose novel therapeutic treatments for these patients. Disclosures No relevant conflicts of interest to declare.

Speciation and changes in male gene expression in Drosophila

Genome ◽  
2020 ◽  
pp. 1-11
Author(s):  
Bahar Patlar ◽  
Alberto Civetta
Keyword(s):  
Gene Expression ◽  
Reproductive Isolation ◽  
Potential Role ◽  
Regulation Of Gene Expression ◽  
Drosophila Model ◽  
Depth Analysis ◽  
The Impact ◽  
Plastic Responses ◽  
Male Gene

It has long been acknowledged that changes in the regulation of gene expression may account for major organismal differences. However, we still do not fully understand how changes in gene expression evolve and how do such changes influence organisms’ differences. We are even less aware of the impact such changes might have in restricting gene flow between species. Here, we focus on studies of gene expression and speciation in the Drosophila model. We review studies that have identified gene interactions in post-mating reproductive isolation and speciation, particularly those that modulate male gene expression. We also address studies that have experimentally manipulated changes in gene expression to test their effect in post-mating reproductive isolation. We highlight the need for a more in-depth analysis of the role of selection causing disrupted gene expression of such candidate genes in sterile/inviable hybrids. Moreover, we discuss the relevance to incorporate more routinely assays that simultaneously evaluate the potential effects of environmental factors and genetic background in modulating plastic responses in male genes and their potential role in speciation.

scholarly journals The nucleoplasmic interactions among Lamin A/C-pRB-LAP2α-E2F1 are modulated by dexamethasone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anastasia Ricci ◽  
Sara Orazi ◽  
Federica Biancucci ◽  
Mauro Magnani ◽  
Michele Menotta
Keyword(s):  
Gene Expression ◽  
Cell Cycle Progression ◽  
Regulation Of Gene Expression ◽  
Lamin A ◽  
Wild Type ◽  
Cycle Progression ◽  
C Dynamics ◽  
E2f Transcription Factor ◽  
Transcription Factor 1

AbstractAtaxia telangiectasia (AT) is a rare genetic neurodegenerative disease. To date, there is no available cure for the illness, but the use of glucocorticoids has been shown to alleviate the neurological symptoms associated with AT. While studying the effects of dexamethasone (dex) in AT fibroblasts, by chance we observed that the nucleoplasmic Lamin A/C was affected by the drug. In addition to the structural roles of A-type lamins, Lamin A/C has been shown to play a role in the regulation of gene expression and cell cycle progression, and alterations in the LMNA gene is cause of human diseases called laminopathies. Dex was found to improve the nucleoplasmic accumulation of soluble Lamin A/C and was capable of managing the large chromatin Lamin A/C scaffolds contained complex, thus regulating epigenetics in treated cells. In addition, dex modified the interactions of Lamin A/C with its direct partners lamin associated polypeptide (LAP) 2a, Retinoblastoma 1 (pRB) and E2F Transcription Factor 1 (E2F1), regulating local gene expression dependent on E2F1. These effects were differentially observed in both AT and wild type (WT) cells. To our knowledge, this is the first reported evidence of the role of dex in Lamin A/C dynamics in AT cells, and may represent a new area of research regarding the effects of glucocorticoids on AT. Moreover, future investigations could also be extended to healthy subjects or to other pathologies such as laminopathies since glucocorticoids may have other important effects in these contexts as well.

scholarly journals The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

scholarly journals Cryptic Transcription and Early Termination in the Control of Gene Expression

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Jessie Colin ◽  
Domenico Libri ◽  
Odil Porrua
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Regulatory Function ◽  
Large Set ◽  
Control Of Gene Expression ◽  
Alternative Transcription ◽  
Cryptic Transcription ◽  
Nuclear Exosome ◽  
The Impact

Recent studies on yeast transcriptome have revealed the presence of a large set of RNA polymerase II transcripts mapping to intergenic and antisense regions or overlapping canonical genes. Most of these ncRNAs (ncRNAs) are subject to termination by the Nrd1-dependent pathway and rapid degradation by the nuclear exosome and have been dubbed cryptic unstable transcripts (CUTs). CUTs are often considered as by-products of transcriptional noise, but in an increasing number of cases they play a central role in the control of gene expression. Regulatory mechanisms involving expression of a CUT are diverse and include attenuation, transcriptional interference, and alternative transcription start site choice. This review focuses on the impact of cryptic transcription on gene expression, describes the role of the Nrd1-complex as the main actor in preventing nonfunctional and potentially harmful transcription, and details a few systems where expression of a CUT has an essential regulatory function. We also summarize the most recent studies concerning other types of ncRNAs and their possible role in regulation.

scholarly journals Function of cofactor Akirin2 in the regulation of gene expression in model human Caucasian neutrophil-like HL60 cells

2021 ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Margarita Villar ◽  
Agustín Estrada-Peña ◽  
Adrián Velázquez-Campoy ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Transcriptional Activation ◽  
Regulation Of Gene Expression ◽  
Regulatory Function ◽  
Biological Processes ◽  
Protein Targets ◽  
Chromatin Remodelers ◽  
Hl60 Cells ◽  
Associated Proteins

The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In this study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple biological processes with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression.

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