Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes

Ghaedi, Hamid; Bastami, Milad; Zare‐Abdollahi, Davood; Alipoor, Behnam; Movafagh, Abolfazl; Mirfakhraie, Reza; Omrani, Mir Davood; Masotti, Andrea

doi:10.1016/j.ygeno.2015.10.004

Cited by 24 publications

(21 citation statements)

References 37 publications

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“…Involvement of miRNAs in the negative regulation of downstream genes affects multiple target mRNAs of important cellular processes (Ghaedi et al, ). DNA methylation and miRNA are important epigenetic markers that affect gene expression in cancerous cells (Loginov et al, ).…”

Section: Introductionmentioning

confidence: 99%

Aberrant miRNA promoter methylation and EMT‐involving miRNAs in breast cancer metastasis: Diagnosis and therapeutic implications

Zare

Bastami

Solali

et al. 2017

Journal Cellular Physiology

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Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis. The miRNAs are related to epigenetic event and additionally affect epigenetic pathways. Recent evidence demonstrates that epigenetic mechanisms such as DNA methylation may control miRNA expression. Because each miRNA may regulate several target genes, dysregulation of miRNA caused by aberrant DNA methylation patterns of the locus may influence important downstream pathways. Furthermore, some miRNAs is believed to regulate important DNA methylator factors. Any disruption or modification of this intricate network can contribute to the disease process; thus, it is essential to understand these changes. Advancements in new sequencing technologies to detect DNA methylation patterns has provided the opportunity to determine differentially methylated regions (DMRs) of the miRNA locus and their effect on expression profiles to improve BC diagnosis and treatment. The current review examines the interplay of DNA methylation mechanisms and miRNA function in invasive tumorigenesis, specifically EMT and CSC of BC, to highlight its potential for advancements on BC etiology, diagnosis, and therapy.

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Section: Introductionmentioning

confidence: 99%

Aberrant miRNA promoter methylation and EMT‐involving miRNAs in breast cancer metastasis: Diagnosis and therapeutic implications

Zare

Bastami

Solali

et al. 2017

Journal Cellular Physiology

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“…Gelsolin is a ubiquitous actin filament-severing protein, one of the most important members of the actin-severing superfamily, and plays a crucial role in the regulation of actin filament assembly and disassembly. Additionally, it has an important responsibility in many other cellular properties, such as carcinogenesis phenotypes, epithelial-mesenchymal transition (EMT), motility, apoptosis, proliferation, and differentiation [24][25][26]. GSN overexpression has been seen in many cancers, including breast cancer, oral carcinoma cells, colorectal cancer, ovarian cancer, and leukemia [27][28].…”

Section: Discussionmentioning

confidence: 99%

Application of an Artificial Neural Network in the Diagnosis of Chronic Lymphocytic Leukemia

Aghamaleki¹,

Mollashahi²,

Nosrati³

et al. 2019

Cureus

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Introduction Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia, and the early diagnosis of patients coincides with their proper treatment and survival. If patients are diagnosed late or proper treatment is not applied, it may lead to harmful results. Several methods could be used for the diagnosis of leukemia; some of these include complete blood count (CBC), immunophenotyping, lymph node biopsy, chest X-ray, computerized tomography (CT) scan, and ultrasound. Most of these methods are time-consuming and an application of more than one method will result as intended. This acknowledgment stresses the necessity of rapid and proper diagnosis for leukemia based on clinical and medical findings, inasmuch as it was decided to apply the artificial neural network (ANN) in order to identify a molecular biomarker for rapid leukemia diagnosis from blood samples and evaluate its potential for the detection of cancer. Materials & methods The independent sample t-test was applied with the Statistical Package for the Social Sciences (SPSS; IBM Corp, Armonk, NY, US) software on the microarray gene expression data of Gene Expression Omnibus (GEO) datasets (GSE22529); 12 genes that had shown the highest differences (among parameters whose p-value was less than 0.01) were selected for further ANN analysis. The selected genes of 53 patients were applied to the training network algorithm, with a learning rate of 0.1. Results The results showed a high accuracy of the relationship between the output of the trained network and the test data. The area under the receiver operating characteristic (ROC) curve was 0.991, which provides proof of the precision and the relationship with identifying Gelsolin as a potential biomarker for this research. Conclusions With these results, it was concluded that the training process of the ANN could be applied to rapid CLL diagnosis and finding a potential biomarker. Besides, it is suggested that this method could be performed to diagnose other forms of cancer in order to get a rapid and reliable outcome.

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“…MiRNA expression is highly dependent on the cell type and developmental stage of myeloid cells [ 56 ]. Next to the deregulation of miRNAs in hematologic disorders, genetic variations in miRNAs, such as SNPs and single nucleotide variants (SNV) are able to disrupt the miRNA target interaction [ 57 ] or causing loss of miRNA expression [ 58 ]. These disrupting SNVs/SNPs might also play a role in MDS and/or sAML as shown for other cancers [ 59 ].…”

Section: Characteristics Of Mirnasmentioning

confidence: 99%

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

Bauer

Vaxevanis

Heimer

et al. 2020

IJMS

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Myelodysplastic syndromes (MDS), heterogeneous diseases of hematopoietic stem cells, exhibit a significant risk of progression to secondary acute myeloid leukemia (sAML) that are typically accompanied by MDS-related changes and therefore significantly differ to de novo acute myeloid leukemia (AML). Within these disorders, the spectrum of cytogenetic alterations and oncogenic mutations, the extent of a predisposing defective osteohematopoietic niche, and the irregularity of the tumor microenvironment is highly diverse. However, the exact underlying pathophysiological mechanisms resulting in hematopoietic failure in patients with MDS and sAML remain elusive. There is recent evidence that the post-transcriptional control of gene expression mediated by microRNAs (miRNAs), long noncoding RNAs, and/or RNA-binding proteins (RBPs) are key components in the pathogenic events of both diseases. In addition, an interplay between RBPs and miRNAs has been postulated in MDS and sAML. Although a plethora of miRNAs is aberrantly expressed in MDS and sAML, their expression pattern significantly depends on the cell type and on the molecular make-up of the sample, including chromosomal alterations and single nucleotide polymorphisms, which also reflects their role in disease progression and prediction. Decreased expression levels of miRNAs or RBPs preventing the maturation or inhibiting translation of genes involved in pathogenesis of both diseases were found. Therefore, this review will summarize the current knowledge regarding the heterogeneity of expression, function, and clinical relevance of miRNAs, its link to molecular abnormalities in MDS and sAML with specific focus on the interplay with RBPs, and the current treatment options. This information might improve the use of miRNAs and/or RBPs as prognostic markers and therapeutic targets for both malignancies.

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Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes

Cited by 24 publications

References 37 publications

Aberrant miRNA promoter methylation and EMT‐involving miRNAs in breast cancer metastasis: Diagnosis and therapeutic implications

Aberrant miRNA promoter methylation and EMT‐involving miRNAs in breast cancer metastasis: Diagnosis and therapeutic implications

Application of an Artificial Neural Network in the Diagnosis of Chronic Lymphocytic Leukemia

Expression, Regulation and Function of microRNA as Important Players in the Transition of MDS to Secondary AML and Their Cross Talk to RNA-Binding Proteins

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