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Transformin Growth Factor-β
Published in Jason Kelley, Cytokines of the Lung, 2022
The amount of active TGF-β released by cells can be regulated at any of the regulatory points from transcriptional control to activation following secretion. Molecular dissection of the TGF-β1 upstream promoter reveals a number of distinct regulatory elements, including an enhancer region, a positive regulatory region, and at least two separate negative regulatory elements. The positive regulatory regions contain binding sites for transcriptional factors, including nuclear factor 1 (NF-1) and others. TGF-β1 and phorbol ester both act through the same regulatory elements of the TGF-β gene (Kim et al., 1989a). There is the option for differential regulation of the different forms of TGF-β.
Sotos Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
It should be noted that mutation in the nuclear factor I/X type gene (NFIX) on chromosome 19p13.3 may produce an autosomal dominant disorder known as Malan syndrome (or Sotos syndrome 2) [11–13]. Nuclear factor I is a ubiquitous 47-kD dimeric DNA-binding protein with the capability of stimulating the transcription of genes in cooperation with other factors such as estrogen receptor (ESR). In addition, alteration in the APC2 gene on chromosome 19p13.3 may cause an autosomal recessive disease known as Sotos syndrome 3. APC2 is a 2303-aa protein gene preferentially expressed in postmitotic neurons. As NSD1 is shown to downregulate APC2 in neurons, it is no surprise that Apc2-deficient (Apc2−/−) mice exhibit impaired learning and memory abilities along with an abnormal head shape [14,15]. Given that the mitogen-activated protein kinase (MAPK) pathway is a diminished activity state in Sotos syndrome, it may be also involved in statural overgrowth and accelerated skeletal maturation [16]. In addition, NSD1 forms as a fusion transcript with NUP98, playing a part in leukemogenesis through H3K36 methylation and subsequent HOX-A gene activation, particularly childhood acute myeloid leukemia [17].
Applications of imaging genomics beyond oncology
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Xiaohui Yao, Jingwen Yan, Li Shen
As with many other complex diseases, a substantial progress in the discovery of genetic factors contributing to the pathology of bipolar disease has been achieved by genome-wide association studies. Testing 1.8 million variants in 4,387 cases and 6,209 controls, Ferreira et al. identified the region of ankyrin 3 (ANK3) and calcium voltage-gated channel subunit alpha1 C (CACNA1C) in strong association with disease risk [138]. The Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) later reported results with an even larger sample size [139] where genotype data were assembled from a combined analysis of 16,731 samples. They successfully confirmed the genome-wide significance of CACNA1C and identified several other genetic regions, such as teneurin transmembrane protein (TENM4 [ODZ4]), ANK3,and spectrin repeat containing nuclear envelope protein 1 (SYNE1), to be related with bipolar. However, in the subsequent replication study with 46,912 samples, only 18 SNPs from CACNA1C and ODZ4 showed significant signals with the same effect direction. Results from a recent GWAS based on Japanese population support nuclear factor I X (NFIX), mitotic arrest deficient 1 like 1 (MAD1L1), tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1), and ODZ4 as susceptible genes associated with bipolar disease risk [140].
Transcription factor ETV1-induced lncRNA MAFG-AS1 promotes migration, invasion, and epithelial–mesenchymal transition of pancreatic cancer cells by recruiting IGF2BP2 to stabilize ETV1 expression
Published in Growth Factors, 2023
Hanqin Weng, Weijian Feng, Fengling Li, Dong Huang, Liangyi Lin, Zaiguo Wang
PC is a common tumor of the digestive system worldwide, characterized by strong migration and aggressiveness (Ilic and Ilic 2016). Although comprehensive treatment has made great achievements, the morbidity and mortality of PC are still growing, which constitutes a serious threat to human life and health (Chu, Goggins, and Fishman 2017). LncRNAs are widely believed to govern the biological progression of many cancers (Hu et al. 2020). Specifically, MAFG-AS1 promotes nuclear factor I X by sponging miR-3196, thereby exacerbating the progression of PC (Heeg et al. 2016). Yet, the specific mechanism of MAFG-AS1 in PC has not been elucidated so far. Our findings demonstrated that ETV1-induced lncRNA MAFG-AS1 stabilized ETV1 expression and promoted PC cell proliferation, migration, invasion, and EMT by recruiting IGF2BP2.
HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus
Published in Gynecological Endocrinology, 2020
Selvihan Beysel, Ferda Alparslan Pinarli, Nilnur Eyerci, Muhammed Kizilgul, Sema Hepsen, Ali Alhan, Seyfullah Kan, Mustafa Caliskan, Erhan Bozkurt, Erman Cakal
The fat mass and obesity-associated gene (FTO) rs9939609 single nucleotide polymorphism (SNPs) has been associated with obesity and type 2 DM [5,8]. The effects of the FTO gene on the increased risk of type 2 DM is mediated by body mass index (BMI) [5]. The association of the FTO gene with GDM and preeclampsia remains unclear. Hepatocyte nuclear factor 1 A (HNF1α), a transcription factor, has a role in ß-cell development [9]. Endocrine and exocrine pancreatic cells express HNF1α in the developmental stage, thus HNF1α is necessary for the glucose response to insulin secretion and glucose metabolism [10]. Women with HNF1α gene mutations were diagnosed as having the monogenic form of DM as maturity-onset diabetes of the young type 3 (MODY3) and usually present with GDM, subsequently, diabetes persists postpartum for several years [11,12]. HNF1α gene SNPs were associated with an increased risk of having DM [13]. The HNF1α gene has been associated with β-cell function [14–18], but the relation of HNF1α gene SNPs with GDM and preeclampsia remains unclear.
Homozygous familial hypercholesterolemia and its treatment by inclisiran
Published in Expert Opinion on Orphan Drugs, 2020
A David Marais, Dirk J Blom, Frederick J Raal
Since the measurements of PCSK9 have not been fully standardized, reports of concentrations may differ as discussed by Malo et al. in a recent review [25]. Some assays include the inactive furin-cleaved product, which may be about 15% of the mature form in hoFH. Plasma PCSK9 has a short half-life of 5 minutes. This will result in rapid adaptation of LDL receptor activity. The plasma PCSK9 concentration follows a diurnal rhythm, and responds to changes in estrogen such that postmenopausally the concentration of PCSK9 may rise and could at least partially explain the rise in plasma cholesterol concentration postmenopausally. The fasting state, resistin, thyroxin, diet, and exercise also influence the concentration of PCSK9. Apart from statins, fibrates and ezetimibe also increase PCSK9 expression. Regulation of PCSK9 synthesis occurs through a sterol response element in the promoter region of this gene. The response to cholesterol depletion in the intracellular membranes, through a finely tuned process, involves proteolysis and the production of sterol regulatory element binding protein 2 (SREBP2) which then acts on the promoter of the genes in the nucleus of the cell. In addition, there is a cooperating hepatic nuclear factor 1 site that promotes synthesis of PCSK9. PCSK9 may also be activated through the mTORC1 mechanism as indicated in Figure 1. High fructose diets may also increase plasma PCSK9 levels.