scholarly journals Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Sha He ◽  
Haiyan Ou ◽  
Cunyou Zhao ◽  
Jian Zhang
Keyword(s):  
Genetic Variation ◽  
Target Genes ◽  
Current Knowledge ◽  
Seed Region ◽  
Functional Effect ◽  
Mirna Clusters ◽  
Vital Effects ◽  
Computational Analyses ◽  
Clustering Pattern ◽  
Mirna Seed

miRNAs are a class of noncoding RNAs important in posttranscriptional repressors and involved in the regulation of almost every biological process by base paring with target genes through sequence in their seed regions. Genetic variations in the seed regions have vital effects on gene expression, phenotypic variation, and disease susceptibility in humans. The distribution pattern of genetic variation in miRNA seed regions might be related to miRNA function and is worth paying more attention to. We here employed computational analyses to explore the clustering pattern and functional effect of SNPs in human miRNA seed regions. A total of 1879 SNPs were mapped to 1226 human miRNA seed regions. We found that miRNAs with SNPs in their seed region are significantly enriched in miRNA clusters. We also found that SNPs in clustered miRNA seed regions have a lower functional effect than have SNPs in nonclustered miRNA seed regions. Additionally, we found that clustered miRNAs with SNPs in seed regions are involved in more pathways. Overall, our results demonstrate that SNPs in clustered miRNA seed regions can take part in more intricate and complex gene-regulating networks with lower functional cost by functional complementarity. Moreover, our results also broaden current knowledge on the genetic variation in human miRNA seed regions.

scholarly journals How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2611
Author(s):  
Jayron J. Habibe ◽  
Maria P. Clemente-Olivo ◽  
Carlie J. de Vries
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Current Knowledge ◽  
Genetic Regulation ◽  
Regulation Of Gene Expression ◽  
Lim Domain ◽  
Multifactorial Diseases ◽  
Lim Domains ◽  
Age Related

Susceptibility to complex pathological conditions such as obesity, type 2 diabetes and cardiovascular disease is highly variable among individuals and arises from specific changes in gene expression in combination with external factors. The regulation of gene expression is determined by genetic variation (SNPs) and epigenetic marks that are influenced by environmental factors. Aging is a major risk factor for many multifactorial diseases and is increasingly associated with changes in DNA methylation, leading to differences in gene expression. Four and a half LIM domains 2 (FHL2) is a key regulator of intracellular signal transduction pathways and the FHL2 gene is consistently found as one of the top hyper-methylated genes upon aging. Remarkably, FHL2 expression increases with methylation. This was demonstrated in relevant metabolic tissues: white adipose tissue, pancreatic β-cells, and skeletal muscle. In this review, we provide an overview of the current knowledge on regulation of FHL2 by genetic variation and epigenetic DNA modification, and the potential consequences for age-related complex multifactorial diseases.

scholarly journals Cross-Kingdom Regulation by Plant microRNAs Provides Novel Insight into Gene Regulation

2020 ◽  
Author(s):  
Abdul Fatah A Samad ◽  
Mohd Farizal Kamaroddin ◽  
Muhammad Sajad
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Current Knowledge ◽  
Circulatory System ◽  
Dietary Therapy ◽  
Transcriptional Level ◽  
Plant Mirnas ◽  
Health Issues ◽  
Plant Mirna ◽  
Potential Applications

ABSTRACT microRNAs (miRNAs) are well known as major players in mammalian and plant genetic systems that act by regulating gene expression at the post-transcriptional level. These tiny molecules can regulate target genes (mRNAs) through either cleavage or translational inhibition. Recently, the discovery of plant-derived miRNAs showing cross-kingdom abilities to regulate mammalian gene expression has prompted exciting discussions among researchers. After being acquired orally through the diet, plant miRNAs can survive in the digestive tract, enter the circulatory system, and regulate endogenous mRNAs. Here, we review current knowledge regarding the cross-kingdom mechanisms of plant miRNAs, related controversies, and potential applications of these miRNAs in dietary therapy, which will provide new insights for plant miRNA investigations related to health issues in humans.

scholarly journals Genetic Polymorphisms Associated with Spontaneous Intracerebral Hemorrhage

2018 ◽  
Vol 19 (12) ◽  
pp. 3879 ◽  
Author(s):  
Yi-Chun Chen ◽  
Kuo-Hsuan Chang ◽  
Chiung-Mei Chen
Keyword(s):  
Genetic Variation ◽  
Lipid Metabolism ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Vessel Wall ◽  
Current Knowledge ◽  
Gene Variants ◽  
Spontaneous Intracerebral Hemorrhage ◽  
The Difference ◽  
Variance Explained

Differences in the incidence of spontaneous intracerebral hemorrhage (ICH) between ethnicities exist, with an estimated 42% of the variance explained by ethnicity itself. Caucasians have a higher proportion of lobar ICH (LICH, 15.4% of all ICH) than do Asians (3.4%). Alterations in the causal factor exposure between countries justify part of the ethnic variance in ICH incidence. One third of ICH risk can be explained by genetic variation; therefore, genetic differences between populations can partly explain the difference in ICH incidence. In this paper, we review the current knowledge of genetic variants associated with ICH in multiple ethnicities. Candidate gene variants reportedly associated with ICH were involved in the potential pathways of hypertension, vessel wall integrity, lipid metabolism, endothelial dysfunction, inflammation, platelet function, and coagulopathy. Furthermore, variations in APOE (in multiple ethnicities), PMF1/SLC25A44 (in European), ACE (in Asian), MTHFR (in multiple ethnicities), TRHDE (in European), and COL4A2 (in European) were the most convincingly associated with ICH. The majority of the associated genes provide small contributions to ICH risk, with few of them being replicated in multiple ethnicities.

scholarly journals NANOG expression in human development and cancerogenesis

2020 ◽  
Vol 245 (5) ◽  
pp. 456-464 ◽  
Author(s):  
Gašper Grubelnik ◽  
Emanuela Boštjančič ◽  
Ana Pavlič ◽  
Marina Kos ◽  
Nina Zidar
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Human Development ◽  
Target Genes ◽  
Normal Development ◽  
Current Knowledge ◽  
Precancerous Lesions ◽  
Embryonic Stem ◽  
Predictive Marker ◽  
Nanog Expression

NANOG is an important stem cell transcription factor involved in human development and cancerogenesis. Its expression is complex and regulated on different levels. Moreover, NANOG protein might regulate hundreds of target genes at the same time. NANOG is crucial for preimplantation development phase and progressively decreases during embryonic stem cells differentiation, thus regulating embryonic and fetal development. Postnatally, NANOG is undetectable or expressed in very low amounts in the majority of human tissues. NANOG re-expression can be detected during cancerogenesis, already in precancerous lesions, with increasing levels of NANOG in high grade dysplasia. NANOG is believed to enable cancer cells to obtain stem-cell like properties, which are believed to be the source of expanding growth, tumor maintenance, metastasis formation, and tumor relapse. High NANOG expression in cancer is frequently associated with advanced stage, poor differentiation, worse overall survival, and resistance to treatment, and is therefore a promising prognostic and predictive marker. We summarize the current knowledge on the role of NANOG in cancerogenesis and development, including our own experience. We provide a critical overview of NANOG as a prognostic and diagnostic factor, including problems regarding its regulation and detection. Impact statement NANOG has emerged as a key stem cell transcription factor in normal development and cancerogenesis. It is generally regarded as a good prognostic and predictive factor in various human cancers. It is less known that it is expressed already at precancerous stages in various organs, suggesting that finally an ideal candidate diagnostic marker has been discovered, enabling to distinguish between true dysplasia and reactive atypia. NANOG regulation is complex, and new insights into our understanding of its regulation might provide important information for future development in a broad field of two entirely different processes, i.e. normal development and cancerogenesis, showing how a physiologic mechanism can be used and abused, transforming itself into a key mechanism of disease development and progression.

scholarly journals miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1790 ◽  
Author(s):  
Marta Sereno ◽  
Mafalda Videira ◽  
Imola Wilhelm ◽  
István A. Krizbai ◽  
Maria Alexandra Brito
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Metastatic Cascade ◽  
Physiological Processes ◽  
Breast Cancer Brain Metastasis ◽  
Health And Disease

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

scholarly journals MicroRNA-26a: An Emerging Regulator of Renal Biology and Disease

2019 ◽  
Vol 44 (3) ◽  
pp. 287-297 ◽  
Author(s):  
Xiaoyan Li ◽  
Xiao Pan ◽  
Xianghui Fu ◽  
Yi Yang ◽  
Jianghua Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Mesangial Cells ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Autoimmune Diabetes ◽  
Ischemia Reperfusion ◽  
Biological Processes ◽  
Immune Attack ◽  
Renal System ◽  
And Function

MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that modulate many key biological processes by simultaneously suppressing multiple target genes. Among them, miR-26a, a conserved miRNA among vertebrates, is highly expressed in various tissues. Accumulating evidence demonstrates that miR-26a plays pivotal roles in cellular differentiation, cell growth, apoptosis, and metastasis, thereby participating in the initiation and development of various human diseases, such as metabolic disease and cancer. More recently, miR-26a was found as a versatile regulator of renal biology and disease. miR-26a is intensively involved in the maintenance of podocyte homeostasis and the actin cytoskeleton. It is also able to modulate the homeostasis and function of mesangial cells. In addition, miR-26a affects the expansion of regulatory T cells in the context of ischemia-reperfusion injury and autoimmune diabetes and thus protects the renal system from immune attack. These available data strongly suggest that renal miR-26a possesses critical pathological functions and represents a potential target for renal disease therapies. This review summarizes current knowledge of miR-26a in renal biology and disease, laying the foundation for exploring its previously unknown functions and mechanisms in the renal system.

scholarly journals Systematic Prediction of the Impacts of Mutations in MicroRNA Seed Sequences

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Anindya Bhattacharya ◽  
Yan Cui
Keyword(s):  
Target Genes ◽  
Computational Method ◽  
Seed Region ◽  
Biological Processes ◽  
Crucial Importance ◽  
Single Nucleotide ◽  
Knowledge Based ◽  
Original Target ◽  
Non Coding Rnas ◽  
Comprehensive Reference

AbstractMicroRNAs are a class of small non-coding RNAs that are involved in many important biological processes and the dysfunction of microRNA has been associated with many diseases. The seed region of a microRNA is of crucial importance to its target recognition. Mutations in microRNA seed regions may disrupt the binding of microRNAs to their original target genes and make them bind to new target genes. Here we use a knowledge-based computational method to systematically predict the functional effects of all the possible single nucleotide mutations in human microRNA seed regions. The result provides a comprehensive reference for the functional assessment of the impacts of possible natural and artificial single nucleotide mutations in microRNA seed regions.

scholarly journals MiR-146a/b: a family with shared seeds and different roots

2017 ◽  
Vol 49 (4) ◽  
pp. 243-252 ◽  
Author(s):  
Mark R. Paterson ◽  
Alison J. Kriegel
Keyword(s):  
Target Genes ◽  
Family Members ◽  
Differential Regulation ◽  
Seed Region ◽  
Small Noncoding Rnas ◽  
Specific Effects ◽  
Exciting Potential ◽  
Health And Disease ◽  
Experimental Approaches ◽  
Functional Relevance

MicroRNAs are small, noncoding, RNAs known for their powerful modulation of molecular processes, making them a major focus for studying pathological mechanisms. The human miR-146 family of microRNAs consists of two member genes, MIR146A and MIR146B. These two microRNAs are located on different chromosomes and exhibit differential regulation in many cases. However, they are nearly identical in sequence, sharing a seed region, and are thus predicted to target the same set of genes. A large proportion of the microRNA (miR)-146 literature focuses on its role in regulating the innate immune response in the context of various pathologies by modulating two widely studied target genes in the toll-like receptor signaling cascade. A growing subset of the literature reports a role of miR-146 in cardiovascular and renal disease, and data suggest there is exciting potential for miR-146 as a diagnostic and therapeutic target. Nevertheless, the published literature is confounded by unclear and imprecise language concerning the specific effects of the two miR-146 family members. The present review will compare the genomic origin and regulation of miR-146a and miR-146b, discuss some approaches to overcome analytical and experimental challenges, and summarize findings in major areas of miR-146 research. Moving forward, careful evaluation of miR-146a/b specificity in analytical and experimental approaches will aid researchers in elucidating the functional relevance of differential regulation of the miR-146 family members in health and disease.

scholarly journals An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis

2017 ◽  
Vol 16 ◽  
pp. 117693511771640 ◽  
Author(s):  
Martha L Slattery ◽  
Jennifer S Herrick ◽  
John R Stevens ◽  
Roger K Wolff ◽  
Lila E Mullany
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Colonic Mucosa ◽  
Target Gene ◽  
Target Genes ◽  
Multiple Comparisons ◽  
Normal Colonic Mucosa ◽  
Seed Region ◽  
Discovery Phase

Background: Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes. Methods: We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miRNAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations. Results: From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37, respectively. Conclusions: Our data suggest that miRNA target gene databases are incomplete; pathways derived from these databases have similar deficiencies. Although we know a lot about several miRNAs, little is known about other miRNAs in terms of their targeted genes. We encourage others to use their data to continue to further identify and validate miRNA-targeted genes.

Grainyhead-like Transcription Factors in Craniofacial Development

2017 ◽  
Vol 96 (11) ◽  
pp. 1200-1209 ◽  
Author(s):  
M.R. Carpinelli ◽  
M.E. de Vries ◽  
S.M. Jane ◽  
S. Dworkin
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Current Knowledge ◽  
Craniofacial Development ◽  
Molecular Networks ◽  
Multiple Model ◽  
Therapeutic Measures ◽  
Formation Conditions ◽  
Maxilla And Mandible ◽  
Craniofacial Defects

Craniofacial development in vertebrates involves the coordinated growth, migration, and fusion of several facial prominences during embryogenesis, processes governed by strict genetic and molecular controls. A failure in any of the precise spatiotemporal sequences of events leading to prominence fusion often leads to anomalous facial, skull, and jaw formation—conditions termed craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births, CFDs are a highly heterogeneous class of developmental anomalies, which are often underpinned by genetic mutations. Therefore, identifying novel disease-causing mutations in genes that regulate craniofacial development is a critical prerequisite to develop new preventive or therapeutic measures. The Grainyhead-like ( GRHL) transcription factors are one such gene family, performing evolutionarily conserved roles in craniofacial patterning. The antecedent member of this family, Drosophila grainyhead ( grh), is required for head skeleton development in fruit flies, loss or mutation of Grhl family members in mouse and zebrafish models leads to defects of both maxilla and mandible, and recently, mutations in human GRHL3 have been shown to cause or contribute to both syndromic (Van Der Woude syndrome) and nonsyndromic palatal clefts. In this review, we summarize the current knowledge regarding the craniofacial-specific function of the Grainyhead-like family in multiple model species, identify some of the major target genes regulated by the Grhl transcription factors in craniofacial patterning, and, by examining animal models, draw inferences as to how these data will inform the likely roles of GRHL factors in human CFDs comprising palatal clefting. By understanding the molecular networks regulated by Grhl2 and Grhl3 target genes in other systems, we can propose likely pathways that mediate the effects of these transcription factors in human palatogenesis.

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