Regulation of IGFBP3 gene expression in short children born small for gestational age

Faienza, Maria Felicia; Marzano, Flaviana; Ventura, Alessandro; Wasniewska, Malgorzata; Valenzise, Mariella; Valletti, Alessio; Caratozzolo, Mariano Francesco; Cornacchia, S.; Sbisà, Elisabetta; Tullo, Apollonia

doi:10.1016/j.ghir.2011.09.003

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…These findings indicate that ‐202A/C and ‐185C/T polymorphisms can affect growth hormone response via altering the methylation of IGBP3 promoter . Moreover, the ‐667G/A and ‐185 C/T polymorphisms in IGFBP3 promoter can affect the transcriptional activity of the gene …”

Section: Resultsmentioning

confidence: 82%

DNA methylation and personalized medicine

et al. 2014

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SUMMARYWhat is known and objective: Variation in the expression of drug-response-related genes contributes significantly to interindividual differences in drug response. DNA methylation is one of the most common epigenetic modifications that control gene expression. DNA methylation may occur in genes encoding drug metabolizing enzymes (DMEs), drug transporters and drug targets, and can thereby alter the pharmacokinetics and pharmacodynamics of drugs. In this review, we discuss recent advances in pharmacoepigenetics with a focus on DNA methylation. Methods: The literature search focusing on DNA methylation of drug-response-related genes and DNA methylation-related SNPs in pharmacogenomics was carried out using the PUBMED database and a combination of keywords including DNA methylation, drug response, DMEs, drug transporters, drug target and SNPs. Results and discussion: An extensive range of research has contributed to our understanding of how DNA methylation of drug-response-related genes alters their function. This is particularly well studied in cancer chemotherapy and drug resistance. The impact of polymorphisms of miRNAs in these processes requires further study. What is new and conclusion: DNA methylation-related genetic variation is an increasingly recognized mechanism for altered drug-response and disease susceptibility. These new discoveries require assimilation into the practice of personalized medicine. WHAT IS KNOWN AND OBJECTIVEInterest in the epigenetic modification of genomes has grown exponentially in recent years. Epigenetics plays an important role in regulating gene expression. DNA methylation, the biological methylation of specific nucleotides by DNA methyltransferases (DNMTs), is the epigenetic modification that has attracted most interest. DNA methylation can result in suppression of gene expression, a process that can be reactivated by demethylation.DNA methylation occurs mainly as 5-methylcytosine (5-mC), with a small fraction of N6-methylpurine (N6-mA) and 7-methylguanine (7-mG). Clusters of cytosine-phosphate-guanine dinucleotides in a chromosomal region are referred to as CpG islands. In mammalian genomes, there are about 40 000 CpG islands, which are typically located in the promoters or in the first exon of the genes.1,2 CpG island methylation is a dynamic epigenetic process during mammalian development and is critical in regulating gene expression, 3 maintaining the stability of the genome and its chromosomal structure, 4 and inactivating genomic imprinting and X-chromosome dosage. 5Aberrant methylation of the CpG island may also result in human diseases such as cancer, amentia, autoimmunity and diabetes. Therefore, DNA methylation has become an important focus of recent epigenomics research.Understanding of the role of DNA methylation in pathogenesis has led to the development of several drugs targeting DNA methylation. Two DNMT inhibitors, 5-azacitidine 6,7 and decitabine, 8,9 are approved by the U.S. FDA for the treatment of myelodysplastic syndromes (MDS) and haematological malig...

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Section: Resultsmentioning

confidence: 82%

DNA methylation and personalized medicine

et al. 2014

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“…This result is particularly relevant considering that the growth hormone (GH)-Insulin-Like Growth Factors (IGFs)-Insulin-Like Growth Factors Binding Protein 3 (IGFBP3) axis is a key endocrine modulator of prenatal and postnatal growth and metabolism, confirming an alteration of growth pathways. [15,16].…”

Section: Transcriptome Sequencingmentioning

confidence: 99%

Whole-Exome and Transcriptome Sequencing Expands the Genotype of Majewski Osteodysplastic Primordial Dwarfism Type II

Marzano

Chiara

Consiglio

et al. 2023

IJMS

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Microcephalic Osteodysplastic Primordial Dwarfism type II (MOPDII) represents the most common form of primordial dwarfism. MOPD clinical features include severe prenatal and postnatal growth retardation, postnatal severe microcephaly, hypotonia, and an increased risk for cerebrovascular disease and insulin resistance. Autosomal recessive biallelic loss-of-function genomic variants in the centrosomal pericentrin (PCNT) gene on chromosome 21q22 cause MOPDII. Over the past decade, exome sequencing (ES) and massive RNA sequencing have been effectively employed for both the discovery of novel disease genes and to expand the genotypes of well-known diseases. In this paper we report the results both the RNA sequencing and ES of three patients affected by MOPDII with the aim of exploring whether differentially expressed genes and previously uncharacterized gene variants, in addition to PCNT pathogenic variants, could be associated with the complex phenotype of this disease. We discovered a downregulation of key factors involved in growth, such as IGF1R, IGF2R, and RAF1, in all three investigated patients. Moreover, ES identified a shortlist of genes associated with deleterious, rare variants in MOPDII patients. Our results suggest that Next Generation Sequencing (NGS) technologies can be successfully applied for the molecular characterization of the complex genotypic background of MOPDII.

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“…Considering that IGFBP3 plays a role in several different contexts, its expression is regulated by many factors. In a previous study, we demonstrated that some polymorphisms in the IGFBP3 promoter region, such as −667 G/A and −396 C/T, influence the basal transcriptional activity of the IGFBP3 gene in SGA children, although IGFBP3 expression remains in the normal range for age and sex ( Faienza et al. , 2011 ).…”

Section: Introductionmentioning

confidence: 99%

The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age

Marzano

Ventura

Caratozzolo

et al. 2015

MBoC

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It is demonstrated that IGFBP3 is a direct p73 target gene and that mRNA expression levels of p73 and IGFBP3 are significantly lower in small for gestational age (SGA) children compared with controls; in particular, p73 mRNA expression is significantly lower in SGA children with respect to length, suggesting that p73 is a good biomarker of the clinical risk for SGA children to remain short into adulthood.

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Regulation of IGFBP3 gene expression in short children born small for gestational age

Cited by 6 publications

References 26 publications

DNA methylation and personalized medicine

DNA methylation and personalized medicine

Whole-Exome and Transcriptome Sequencing Expands the Genotype of Majewski Osteodysplastic Primordial Dwarfism Type II

The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age

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