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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The MS2 VLPs were used to encapsulate the long noncoding MEG3 lncRNA and were crosslinked with the GE11 polypeptide, proving beneficial to cancer therapy (Chang L et al. 2016). Nevertheless, the technical problems of crosslinking provoked the team to switch to the phage display technique (Wang Guojing et al. 2016). This was the first study in which the cell-penetrating peptides were displayed on the MS2 VLP surface by genetic fusion. Therefore, the MS2 VLP-based microRNA delivery system was combined for the first time with the phage surface display platform. It is necessary to mention that the HIV TAT peptide was the first reported cell penetrating peptide, since the TAT region 47–57 functioned as the clear protein transduction domain and possessed efficient transport capacity. Therefore, the TAT 47–57 peptide was displayed on the MS2 VLPs by genetic fusion instead of chemical crosslinking. As a result, the TAT peptide was connected to the N-terminus of the single-chain dimer of the MS2 coat, whereas the pre-miR122 was designed with a pac site to facilitate packaging. The study acknowledged not only the cell-penetrating capability of the MS2 VLPs displaying TAT peptide but also the inhibitory effect of the encapsulated miR-122 on the hepatocellular carcinoma cells (Wang Guojing et al. 2016). It seems worth mentioning that a solid article on the cell-specific delivery of mRNA and microRNA by MS2 VLPs carrying cell-penetrating peptides (Sun Yanli and Yin 2015) was retracted at that time.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: the chromosomal region 14q32–14q32.33 is one of those subject to genomic imprinting, an epigenetic germline modification that determines differences in gene expression depending on parental origin. Uniparental disomy (UPD) describes the situation in which both homologs of a chromosome pair are inherited exclusively from one parent and results in overexpression of some genes and absence of expression of others. Consequently paternal and maternal uniparental disomy for chromosome 14 (UPD(14)pat and UPD(14)mat) cause distinct phenotypes. Among the paternally expressed genes (PEGs) are DLK1 and RTL1, while among the maternally expressed genes (MEGs) are MEG3 (or GTL2), RTL1 as (RTL1 antisense) and MEG8. Most cases of UPD14 are secondary to abnormal segregation at meiosis of a paternal Robertsonian translocation, resulting in a trisomic zygote with the subsequent loss of one of the three copies of the chromosome involved (trisomy rescue).
Epigenetics, Nutrition, and Infant Health
Published in Crystal D. Karakochuk, Kyly C. Whitfield, Tim J. Green, Klaus Kraemer, The Biology of the First 1,000 Days, 2017
Philip T. James, Matt J. Silver, Andrew M. Prentice
Several studies describe associations between maternal one-carbon metabolites and infant growth-related outcomes, for example, vitamin B12 [92], folate [93], and homocysteine [94]. What then is the evidence that these associations are mediated through epigenetic mechanisms? Preliminary evidence from the Dutch Hunger Winter, as described earlier, suggests that exposure to famine in pregnancy, particularly around conception, is associated with differential methylation in genes linked to growth, and development [41], and that famine exposure is also related to a wide range of offspring cognitive health and cardiometabolic risk factors six decades later [95]. It is, however, difficult to establish the direction of causality, since disease states can also influence the epigenome [96]. This issue of reverse causality is particularly pertinent to studies using a retrospective cohort design. Stronger evidence comes from prospective cohorts, such as the Newborn Epigenetics Study (NEST) in the United States. Hoyo et al. describe a positive association between maternal folate levels in the first trimester and birth weight [90]. Increased maternal folate was also associated with increased methylation at MEG3, PLAGL1, and PEG3 in infant cord blood, and decreased methylation at IGF2. Five differentially methylated sites were associated with birth weight, and it was speculated that the association seen between maternal folate and birth weight could be mediated by differential methylation at MEG3, H19, and PLAGL1. In a more recent study from the same cohort, McCullough et al. found maternal plasma concentrations of homocysteine in the first trimester were inversely associated with birth weight, particularly in males [97]. Children born to mothers with the highest quartile of plasma B12 showed lower weight gain between birth and 3 years. However, only maternal vitamin B6 was positively associated with cord methylation at a DMR from MEG3. A further example comes from Godfrey et al., who found that higher methylation of RXRA and eNOS in umbilical cord tissue was associated with offspring adiposity at age 9, and that higher RXRA methylation was also associated with lower maternal carbohydrate intake in early pregnancy [91].
Aberrant expression of BAX, MEG3, and miR-214-3P genes in recurrent pregnancy loss
Published in Gynecological Endocrinology, 2021
Saja Al-Rubaye, Sayyed Mohammad Hossein Ghaderian, Saghar Salehpour, Tayyebali Salmani, Samaneh Vojdani, Rusul Yaseen, Reza Akbarzadeh
The ncRNAs such as miRNAs and LncRNAs regulate gene expression in a wide range of important biological processes and can act as prognostic biomarkers in a variety of diseases [20]. Due to the numerous functions of LncRNAs in the maternal-fetal communication system, they might be involved in the physiological and pathogenic processes of RPL. Of note, LncRNAs have been reported to be important in the pathogenesis of unexplained recurrent spontaneous abortion [21]. Moreover, LncRNAs-regulated inflammatory pathways might be involved in pregnancy loss [22]. MEG3, a LncRNA located on human chromosome 14q32, is expressed in many tissues, including the placenta [23]. There is no report to our knowledge indicating the altered expression of MEG3 in RPL. Our results in the present study confirmed a reduced expression level of the MEG3 gene in RPL samples compared to the controls. Furthermore, a negative correlation was noticed between MEG3 and BAX genes in RPL samples. Similar to our study, the reduced expression of MEG3 was reported in placental vascular diseases [24]. In line with this, it has been shown that down-regulation of MEG3 could affect the expression of apoptotic genes such as BAX in trophoblast cells [23].
Silencing MEG3 protects PC12 cells from hypoxic injury by targeting miR-21
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Long non-coding RNAs (lncRNAs) are defined as an important group of transcripts that are longer than 200 nt and have no protein-coding capabilities. In recent years, multiple studies have indicated lncRNAs as vital regulators in a variety of diseases associated with neurological, autoimmune, and cardiovascular conditions [3–5]. Moreover, substantial evidence suggests that lncRNAs can regulate cellular growth, death, or other phenotypes [6]. One important mechanism of lncRNAs’ function is owing to theirs binding effects with microRNAs (miRNAs), which are able to regulate gene expression post-transcriptionally [7]. Maternally expressed gene 3 (MEG3), one of the most important cancer-associated lncRNAs, also known as GTL2, was initially identified on chromosome 12 of the distal mouse. MEG3 is localised on human chromosome 14q32 and is approximately 1.6 kb in length, producing alternative spliced transcripts. Similar to its mouse homologues, the expression and regulation of MEG3 is crucial for embryonic development and growth. Increasing number of literatures highlight MEG3 as an emerging target for HIBD, as high expression level of MEG3 has been found in various kind of brain injury model, like rat middle cerebral artery occlusion (MCAO) [8], oxygen-glucose deprivation and reoxygenation (OGD/R)-injured N2a cells [9], and OGD-injured HT22 cells [10]. Moreover, silence of MEG3 exerted protective functions during HIBD, and MEG3 down-regulation mediated by the specific shRNA has been considered as a new strategy for this disease [11].
New insight into the role of long non-coding RNAs in the pathogenesis of preeclampsia
Published in Hypertension in Pregnancy, 2019
Mohammad-Taher Moradi, Zohreh Rahimi, Asad Vaisi-Raygani
It revealed that dysregulation of MEG3 is involved in PE pathogenesis, probably, by affecting the TGF-β/SMAD signaling pathway (27). The TGF-β/SMAD signaling pathway plays an important role in a variety of biological functions such as development, differentiation, EMT, cell-cycle control, and apoptosis (70). Increased expression of Smad7 blocks TGF-β pathway in multiple tissues while Smad2 and Smad3 in cooperation with Smad4 act as TGF-β-induced transcription regulator (71). Yu et al. comparing preeclamptic placenta with normal placenta showed that the expression level of TGF-β1 and smad-3 protein was significantly higher and the expression of smad-7 (a TGF- β pathway inhibitor) was significantly lower in the preeclampsia group (27).