PDF(Pubmed)
Abstract：
UNASSIGNED: The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases FUT2 and FUT3 mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of FUT2 and FUT3.
UNASSIGNED: To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for FUT2 and FUT3 and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase FUT2 and FUT3 transcription and translation upon interaction.
UNASSIGNED: Understanding the regulation of FUT2 and FUT3 is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.
The Lewis (Le) blood group system, in contrast to the majority of blood groups, is not able to synthesize its antigens itself. It depends on the attachment of different oligosaccharides to the erythrocyte membrane, which are adsorbed from the plasma. These glycans are modified by the fucosyltransferases 2 and 3 enzymes (FUT2/3). Beside their role in defining the Lewis blood group, FUT2 and FUT3 are also known to be involved in the susceptibility and progression of various gastrointestinal pathologies, like inflammatory bowel diseases (IBD) or colorectal cancer (CRC). Even though different expression levels of FUT2 and FUT3 have been described in these malignancies, relatively little is known about the mechanisms behind their transcriptional regulation. In this review, we aim to shed light on transcription factors (TFs) responsible for FUT2 and FUT3 expression as well as on post-transcriptional regulators by the means of RNA binding proteins (RBPs) and microRNAs (miRNAs). To achieve our goal, we combined previous knowledge on FUT2 and FUT3 expression regulation with a computational analysis to predict additional novel regulators. On this way, we are able to broaden our knowledge on FUT2 and FUT3 expression regulation and consequently might be able to transfer our findings into diagnostics or therapeutics in the future.
UNASSIGNED: To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for FUT2 and FUT3 and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase FUT2 and FUT3 transcription and translation upon interaction.
UNASSIGNED: Understanding the regulation of FUT2 and FUT3 is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.
The Lewis (Le) blood group system, in contrast to the majority of blood groups, is not able to synthesize its antigens itself. It depends on the attachment of different oligosaccharides to the erythrocyte membrane, which are adsorbed from the plasma. These glycans are modified by the fucosyltransferases 2 and 3 enzymes (FUT2/3). Beside their role in defining the Lewis blood group, FUT2 and FUT3 are also known to be involved in the susceptibility and progression of various gastrointestinal pathologies, like inflammatory bowel diseases (IBD) or colorectal cancer (CRC). Even though different expression levels of FUT2 and FUT3 have been described in these malignancies, relatively little is known about the mechanisms behind their transcriptional regulation. In this review, we aim to shed light on transcription factors (TFs) responsible for FUT2 and FUT3 expression as well as on post-transcriptional regulators by the means of RNA binding proteins (RBPs) and microRNAs (miRNAs). To achieve our goal, we combined previous knowledge on FUT2 and FUT3 expression regulation with a computational analysis to predict additional novel regulators. On this way, we are able to broaden our knowledge on FUT2 and FUT3 expression regulation and consequently might be able to transfer our findings into diagnostics or therapeutics in the future.
摘要：
■刘易斯（Le）血型系统，与大多数其他血型不同，不是由红细胞内部产生的抗原及其前体定义，而是由血浆吸附到红细胞膜上的聚糖抗原定义。这些寡糖主要由两种岩藻糖基转移酶FUT2和FUT3在消化道的上皮细胞中合成并转移到血浆中。在他们合成的地方，一些Lewis血型糖抗原变体似乎也与各种胃肠道恶性肿瘤有关。然而,对FUT2和FUT3的转录调控知之甚少。
■为了解决这个问题，我们筛选了现有文献,并额外使用了计算机模拟预测工具来确定FUT2和FUT3的新候选调控因子,并将这些发现与已知的调控数据结合起来.通过这种方法，我们能够描述各种转录因子，RNA结合蛋白和microRNA,在相互作用时增加FUT2和FUT3的转录和翻译。
■了解FUT2和FUT3的调节对于充分了解血型系统Lewis（ISBT007LE）表型至关重要，阐明不同的Lewis抗原在各种病理中的作用，并确定这些疾病的潜在新诊断目标。
Lewis(Le)血型系统,与大多数血型相反，本身不能合成它的抗原。它取决于不同寡糖在红细胞膜上的附着，从血浆中吸附。这些聚糖被岩藻糖基转移酶2和3酶(FUT2/3)修饰。除了他们在定义刘易斯血型方面的作用，FUT2和FUT3也已知与各种胃肠道病理的易感性和进展有关。例如炎症性肠病（IBD）或结直肠癌（CRC）。尽管FUT2和FUT3在这些恶性肿瘤中的表达水平不同，对其转录调控背后的机制知之甚少。在这次审查中,我们的目标是通过RNA结合蛋白（RBP）和microRNAs（miRNA）来阐明负责FUT2和FUT3表达的转录因子（TFs）以及转录后调节因子。为了实现我们的目标，我们将先前关于FUT2和FUT3表达调控的知识与计算分析相结合，以预测其他新型调控因子。在这条路上,我们能够拓宽我们对FUT2和FUT3表达调控的认识,从而有可能在未来将我们的发现转化为诊断或治疗.
■为了解决这个问题，我们筛选了现有文献,并额外使用了计算机模拟预测工具来确定FUT2和FUT3的新候选调控因子,并将这些发现与已知的调控数据结合起来.通过这种方法，我们能够描述各种转录因子，RNA结合蛋白和microRNA,在相互作用时增加FUT2和FUT3的转录和翻译。
■了解FUT2和FUT3的调节对于充分了解血型系统Lewis（ISBT007LE）表型至关重要，阐明不同的Lewis抗原在各种病理中的作用，并确定这些疾病的潜在新诊断目标。
Lewis(Le)血型系统,与大多数血型相反，本身不能合成它的抗原。它取决于不同寡糖在红细胞膜上的附着，从血浆中吸附。这些聚糖被岩藻糖基转移酶2和3酶(FUT2/3)修饰。除了他们在定义刘易斯血型方面的作用，FUT2和FUT3也已知与各种胃肠道病理的易感性和进展有关。例如炎症性肠病（IBD）或结直肠癌（CRC）。尽管FUT2和FUT3在这些恶性肿瘤中的表达水平不同，对其转录调控背后的机制知之甚少。在这次审查中,我们的目标是通过RNA结合蛋白（RBP）和microRNAs（miRNA）来阐明负责FUT2和FUT3表达的转录因子（TFs）以及转录后调节因子。为了实现我们的目标，我们将先前关于FUT2和FUT3表达调控的知识与计算分析相结合，以预测其他新型调控因子。在这条路上,我们能够拓宽我们对FUT2和FUT3表达调控的认识,从而有可能在未来将我们的发现转化为诊断或治疗.
