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Beckwith–Wiedemann Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Jirat Chenbhanich, Sirisak Chanprasert, Wisit Cheungpasitporn
As molecular techniques are becoming more advanced and affordable, more children with BWS will be readily diagnosed, and novel molecular etiologies will be uncovered for both familial and sporadic cases. Over the next few years, we expect that testing modalities will more accurately reflect the actual number of BWS cases and help expand the syndrome phenotypic spectrum and natural history. Although the IGF2 and CDKN1C genes are well characterized, their interaction and downstream effectors need to be investigated to explain why disruption in either independent locus results in similar clinical features. Studies on the tumor-suppressor role of H19 RNA transcript are warranted. More research involving the regulation of chromosome 11p15.5 imprinting region as well as other imprinting clusters, and the exact frequency and molecular mechanism of multilocus imprinting disorders are critical to better understand how epigenome affects human health. One of the most important unanswered questions is what mechanism drives a tumor development in a particular subset of BWS patients. Until we can answer that question, we need more data on clinical and genetic heterogeneities to develop a better tool for complete ascertainment of BWS cases, to delineate a more detailed (epi)genotype–phenotype correlation, and to differentiate proper follow-up approaches, tumor risk estimates, and tumor screening protocols ideally based on each molecular subtype.
The Role of Nutraceuticals in the Placental Growth, Development and Function
Published in Priyanka Bhatt, Maryam Sadat Miraghajani, Sarvadaman Pathak, Yashwant Pathak, Nutraceuticals for Prenatal, Maternal and Offspring’s Nutritional Health, 2019
Maryam Miraghajani, Michael E. Symonds
Genomic imprinting as an epigenetic process is responsible for the monoallelic expression of a subset of genes. Indeed, it results in the expression of those genes from only one of the two parental chromosomes. This process has an important role in feto-placental development and function. Adverse imprinting disrupts development and is the cause of various disease syndromes 49–51. For example, IGF2/H19 imprinted genes are associated with fetal growth. In contrast to the paternal expressed of the IGF2, the maternal allele of the mentioned gene is silenced through DNA methylation. The maternally expressed H19 is located downstream of IGF2 encoding a noncoding RNA, which regulates cellular growth. Loss of imprinting leads to reactivation of the silent allele, resulting in biallelic expression and several disorders, such as Angelman syndrome (25) and Prader-Willi syndrome (49).
Genetics of Wilms tumor
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
Mathias A.E. Frevel, Bryan R.G. Williams
The IGF2 gene is one of a number of imprinted genes within a large chromosomal region of 11p15.5 that is hence referred to as an imprinted domain (Reid et al., 1997). The regulation of the monoallelic expression of imprinted genes within this domain involves long ranging chromatin effects and DNA methylation, processes that we know today are interrelated. The investigation of loss of IGF2 imprinting in Wilms tumor and in BWS has greatly contributed to the understanding of imprinting at the 11p15 locus. In the case of Wilms tumor biallelic expression of IGF2 was shown to correlate with silencing and abnormally high DNA methylation of the H19 gene (Moulton et al., 1994; Steenman et al., 1994; Taniguchi et al., 1995). The H19 gene, normally expressed from the maternal allele only, codes for an untranslated RNA of unknown function, and may itself be a growth suppressing gene (Hao et al., 1993). The abnormal methylation of the maternal H19 alleles was shown to effect an upstream region of the gene that is critical for maintaining IGF2 and H19 imprinting (Frevel et al., 1999; Thorvaldsen et al., 1998). This region contains several methylation sensitive binding sites for CTCF (CCCTC-binding factor), an eleven-zinc finger DNA-binding protein that has been shown to bind specific sites between enhancer elements and promotors to prevent gene activation (Bell et al., 1999). On the maternal allele, binding of CTCF to its unmethylated sites blocks the action of downstream enhancers on IGF2 but allows the same enhancers to promote H19 transcription. On the paternal allele, CTCF can not bind to the methylated binding sites, leaving the downstream enhancers free to promote IGF2 transcription (Bell and Felsenfeld, 2000; Hark et al., 2000; Kanduri et al., 2000; Szabo et al., 2000). Aberrant methylation of H19 was also detected in normal kidney tissue from Wilms tumor patients which implies that the epigenetic change occurred very early in kidney development (Okamoto et al., 1997). Taken together, these findings suggest that hypermethylation of HI9, either as a direct cause or in company with other undetected chromatin changes, is responsible for H19 silencing and LOI of IGF2 in Wilms tumors. However, other studies have found that the disruption of the monoallelic expression of H19 and IGF2 in Wilms tumors can also be independent events (Cui et al., 1997; Ohlsson et al., 1999). Finally, it is important to note that only approximately one third of Wilms tumors present maternal 11p15 LOH and another third LOI of IGF2, whereas one third of Wilms tumors exhibit normal monoallelic IGF2 expression. In this latter group other genetic changes may substitute for the consequences of aberrant IGF2 imprinting.
Dysregulation of lncRNA-H19 in cardiometabolic diseases and the molecular mechanism involved : a systematic review
Published in Expert Review of Molecular Diagnostics, 2021
Ana Iris Hernández-Aguilar, Carlos Aldair Luciano-Villa, Vianet Argelia Tello-Flores, Fredy Omar Beltrán-Anaya, Ma Isabel Zubillaga-Guerrero, Eugenia Flores-Alfaro
The molecular mechanisms by which H19 participates in different cardiometabolic diseases are shown in Figure 4. H19 interferes with different pathways that regulate cellular metabolism. In most reports, H19 overexpression is considered a major risk factor, mainly in cardiovascular and liver diseases, while in glucose metabolism disorders it has been demonstrated to have a protective effect. H19 participates in cellular metabolism through the regulation of miRNAs, or as a guide for molecules that regulate the processes in which they interpose. In CVD, H19 has been associated with miR-22-3p, miR-130b, and Let −7 family miRNAs [9,10]. H19 participates in the inflammatory response through the TGF-β, TET-1 and lysine demethylase 3A (KDM3A) pathways, and thus in the development of CAD, such as MI [9,33]. In cardiac fibrosis, H19 plays a role similar to miR-455 in the CTGF and DUSP5 pathways. In most of these pathological processes, H19 is overexpressed, but not with miR-22-3p, where H19 is decreased [28,52].
Long non coding RNA H19: An emerging therapeutic target in fibrosing diseases
Published in Autoimmunity, 2020
Juan Li, Long-Ting Cao, Hong-Hui Liu, Xiao-Dong Yin, Jing Wang
According to a wide lack of expression in normal adult tissue, H19 may, after birth, only play a role in the physiology of cartilage and muscles, tissues. Steck et al. analysed that H19 may not only be an attractive marker for cell anabolism but also a potential target to stimulate cartilage recovery [29]. Importantly, H19 was the first imprinted noncoding transcript to be identified, which can function as a primary miRNA transcript in both humans and mice. These data demonstrate that H19 expression results in the posttranscriptional downregulation of specific mRNAs during vertebrate development [30]. Recently, the role of H19 in epithelial inflammatory response and physiological function has also been described. H19 is likely to play an important role in maintaining normal functions and regulating immune response of bovine mammary epithelial cells by Li et al. [31]. These studies may provide a novel insight to understand the functions of H19.
Quantitative assessment of lncRNA H19 polymorphisms and cancer risk: a meta-analysis based on 48,166 subjects
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Xu Liu, Yating Zhao, Ying Li, Jian Zhang
As a complex disease, cancer becomes a major threat towards worldwide public health [47]. However, the pathogenesis of cancer was still unclear. Although lncRNAs do not encode proteins, they play an important role in human transcription process, especially in cancer-related aspects [48]. Hence, abnormal lncRNA expression may lead to cancer occurrence and development. Large numbers of SNPs have been detected in lncRNAs and many studies focussing on the association between SNPs and cancer susceptibility were performed. H19 is the very first eukaryote lncRNA gene which was found in 1980s, even though it was identified as mRNA at that time [48]. In 2008, Verhaegh et al. reported association between H19 polymorphisms and bladder cancer firstly [27]. Since then, increasingly studies were performed to assess the relationship between H19 polymorphisms (rs217727, rs2839698, rs2107425 and rs3024270) and cancer risk.