Notch Signaling & Micro RNAs - two tumblers of neurogenesis and Gliomas

2020 ◽  
pp. 1-23
Author(s):  
Zeeshan Javed ◽  
Qamar Raza ◽  
Faiez Ahmad Shah ◽  
Haleema Sadia ◽  
Ayesha Alam ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Notch Signaling ◽  
Notch Signalling ◽  
High Rate ◽  
Signaling Cascades ◽  
Signalling Pathways ◽  
Pathological State ◽  
Cellular Processes ◽  
Micro Rnas ◽  
Tumor Suppressor Mirnas

Abstract Gliomas are one of the most annihilating types of brain tumors having a high rate of annual incidence worldwide. Notch signaling is an evolutionary conserved pathway that regulates differentiation and development. Aberrations in Notch signalling pathways lead to severe pathological state such as the Gliomas. MicroRNAs (miRNAs) are the tiny molecules less than 200 bps in length and regulate a myriad of cellular processes. Categorically, miRNAs are divided in to oncogenic and tumor suppressor miRNAs. Accumulating data have identified miRNAs, which positively or negatively regulate Notch signaling in Gliomas. Here, we have assessed status of our understanding of the interplay between miRNA-base regulation of Notch signaling in gliomas, interaction between Notch signaling and other signaling cascades and have also discussed use of natural compounds that will help us get closer to personalized medicine for gliomas. Keywords: Notch signaling; MicroRNA; Therapeutic Targets; Continuous...

scholarly journals Tong-Xie-Yao-Fang improves intestinal permeability in diarrhoea-predominant irritable bowel syndrome rats by inhibiting the NF-κB and notch signalling pathways

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiuke Hou ◽  
Yongquan Huang ◽  
Zhaoyang Zhu ◽  
Liu Liao ◽  
Xinlin Chen ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Intestinal Permeability ◽  
Rat Model ◽  
Distal Colon ◽  
Notch Signalling ◽  
Signalling Pathways ◽  
Model Group ◽  
Related Factors ◽  
Defecation Frequency ◽  
Irritable Bowel

Abstract Background Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. Methods The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. Results After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1β, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). Conclusion TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.

scholarly journals Clinical Importance of Wnt5a in the Pathogenesis of Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mehran Pashirzad ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Clinical Importance ◽  
Signaling Cascades ◽  
Cancer Type ◽  
Invasion And Metastasis ◽  
Cellular Processes ◽  
Wnt5a Expression ◽  
Noncanonical Signaling

Wnt5a is one of the potent signaling molecules that initiates responses involved in cancer through activation of both canonical and noncanonical signaling cascades. Wnt5a both directly and indirectly triggers cancer-associated signaling pathways based on the cancer type. In colorectal cancer (CRC), altering Wnt5a expression can influence several cellular processes of tumor cells, including proliferation, differentiation, migration, invasion, and metastasis. This review summarizes the molecular mechanisms and clinical importance of Wnt5a in the pathogenesis of CRC for better understanding the pathogenesis and its potential role as a prognostic marker and as an appropriate therapeutic target in the treatment of this disease in the future.

scholarly journals Computational Approach to Identify Mutations in Genes of Notch Signaling Pathway and Its Association with OSCC

2020 ◽  
pp. 84-92
Author(s):  
Madhumithaa Sivarajan ◽  
A. S. Smiline Girija ◽  
A. Paramasivam ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Tumor Development ◽  
Suppressor Gene ◽  
Notch Signaling Pathway ◽  
Computational Approach ◽  
Notch Signalling ◽  
Cell Renewal ◽  
Data Set ◽  
The Stability

Derailments in signal transduction pathways are associated with the development of tumors. One such vital pathway is the Notch signaling pathway which is associated with various processes of carcinogenesis such as proliferation of cells, cell renewal, angiogenesis and oncogenic microenvironment preservation. Interestingly, Notch also plays a pivotal role in tumor development by acting as an oncogene as well as tumor suppressor gene. In view of this fact, the present study was designed to analyze mutations in Notch signalling pathway which might have a crucial role in the etiology of oral squamous cell carcinoma (OSCC) using computational approach. The Cancer Gene Atlas data set hosted in the cBioportal was used in the present study. These samples were queried for the presence of mutations in Notch signalling genes which included a predefined list of 55 genes. Further, the Oncoprint data obtained was compared to that of gnomAD database which identified novel and reported mutations in the genes analyzed. Additionally, I-Mutant and MutPred analysis was carried out to determine the stability and pathogenicity of the variations recorded. Among 55 genes analysed, SPEN gene was shown to possess the highest frequency of mutation (5%) followed by FBXW7, Notch1, EP300, NUMB, and RBPJL genes. Most of the mutations identified were novel as assessed using the control dataset from the gnomAD database. The stability of the protein was found to decrease upon nucleotide substitution. Finally, the MutPred score revealed that most of the mutant proteins were pathogenic.  Several novel mutations have been identified in the pathway analyzed. Functional analysis of these variants using experimental approaches would aid in dissecting their association with OSCC.

Interaction of the transforming growth factor-β and Notch signaling pathways in the regulation of granulosa cell proliferation

2016 ◽  
Vol 28 (12) ◽  
pp. 1873 ◽  
Author(s):  
Xiao-Feng Sun ◽  
Xing-Hong Sun ◽  
Shun-Feng Cheng ◽  
Jun-Jie Wang ◽  
Yan-Ni Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Growth Factor ◽  
Granulosa Cell ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Notch Pathway ◽  
Transforming Growth Factor Β ◽  
Notch Signalling ◽  
Signalling Pathways

The Notch and transforming growth factor (TGF)-β signalling pathways play an important role in granulosa cell proliferation. However, the mechanisms underlying the cross-talk between these two signalling pathways are unknown. Herein we demonstrated a functional synergism between Notch and TGF-β signalling in the regulation of preantral granulosa cell (PAGC) proliferation. Activation of TGF-β signalling increased hairy/enhancer-of-split related with YRPW motif 2 gene (Hey2) expression (one of the target genes of the Notch pathway) in PAGCs, and suppression of TGF-β signalling by Smad3 knockdown reduced Hey2 expression. Inhibition of the proliferation of PAGCs by N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signalling, was rescued by both the addition of ActA and overexpression of Smad3, indicating an interaction between the TGF-β and Notch signalling pathways. Co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays were performed to identify the point of interaction between the two signalling pathways. CoIP showed direct protein–protein interaction between Smad3 and Notch2 intracellular domain (NICD2), whereas ChIP showed that Smad3 could be recruited to the promoter regions of Notch target genes as a transcription factor. Therefore, the findings of the present study support the idea that nuclear Smad3 protein can integrate with NICD2 to form a complex that acts as a transcription factor to bind specific DNA motifs in Notch target genes, such as Hey1 and Hey2, and thus participates in the transcriptional regulation of Notch target genes, as well as regulation of the proliferation of PAGCs.

scholarly journals Dysregulation of the ADAM17/Notch signalling pathways in endometriosis: from oxidative stress to fibrosis

2017 ◽  
Vol 23 (7) ◽  
pp. 488-499 ◽  
Author(s):  
Iñaki González-Foruria ◽  
Pietro Santulli ◽  
Sandrine Chouzenoux ◽  
Francisco Carmona ◽  
Charles Chapron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Notch Signalling ◽  
Signalling Pathways

A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and ERp72

2008 ◽  
Vol 416 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Wei Chen ◽  
Wei Hao Shang ◽  
Yoshifumi Adachi ◽  
Kunitaka Hirose ◽  
David M. Ferrari ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Glutathione Transferase ◽  
Mutational Analysis ◽  
Reductase Activity ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Nadph Oxidase 1 ◽  
Endoplasmic Reticulum Protein ◽  
Cellular Context

Emerging evidence indicates that Nox (NADPH oxidase) 1-generated ROS (reactive oxygen species) play critical regulatory roles in various cellular processes, yet little is known of direct targets for the oxidase. In the present study we show that one of the proteins selectively oxidized in response to Nox1-generated ROS was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology domains. Oxidation of ERp72 by Nox1 resulted in an inhibition of its reductase activity. EGF treatment of cells stimulated the Nox1 activity and the activated Nox1 subsequently mediated EGF-induced suppression of the ERp72 reductase activity. Co-immunoprecipitation, GST (glutathione transferase) pulldown assays and mutational analysis, indicated that Nox1 associates with ERp72, which involves its N-terminus encompassing a Ca2+-binding site and the first TRX-like motif. Furthermore, confocal microscopy showed co-localization between Nox1 and ERp72 at the plasma membrane. These results suggest that Nox1 functionally associates with ERp72, regulating redox-sensitive signalling pathways in a cellular context.

Regulation of NLRP3 activation by the ubiquitin system

Inflammasome ◽  
2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Gloria López-Castejón
Keyword(s):  
Nlrp3 Inflammasome ◽  
Protein Modification ◽  
Molecular Complexes ◽  
Signalling Pathways ◽  
Inflammasome Activation ◽  
Immune Disorders ◽  
Cellular Processes ◽  
Ubiquitin System ◽  
Nlrp3 Inflammasome Activation ◽  
Inflammatory Processes

AbstractInflammasomes, molecular complexes activated in response to pathogens or injury, are involved in the activation and release of the proinflammatory cytokine interleukin-1β. Inflammasome activation is tightly controlled and its dysregulation is associated with the development of inflammatory disorders. Ubiquitination, the conjugation of ubiquitin to a protein, is a post-translational protein modification essential for a wide variety of cellular processes. What was initially considered to be just a signal for protein degradation has become a major regulator for signalling pathways that is also involved in the regulation of NLRP3 inflammasome activation. Similarly to the inflammasome, dysregulation of ubiquitin signalling is associated with the initiation and development of pathologies including immune disorders such as arthritis or lupus erythematous, highlighting the relevance of these systems in the inflammatory processes. How the ubiquitin system regulates the NLRP3 inflammasome is discussed here

The role of microRNA in the response to cisplatin treatment

2012 ◽  
Vol 40 (4) ◽  
pp. 821-825 ◽  
Author(s):  
Ross M. Drayton
Keyword(s):  
Protein Expression ◽  
Cisplatin Resistance ◽  
Microrna Expression ◽  
Signalling Pathways ◽  
Cytotoxic Effects ◽  
Cellular Processes

Resistance to the cytotoxic effects of cisplatin can be mediated through changes in a wide variety of cellular processes and signalling pathways. The discovery of microRNAs as regulators of protein expression through the targeting of mRNA has led to a number of studies on the effect of cisplatin treatment on microRNA expression, and the ability of microRNAs to modulate cisplatin resistance.

scholarly journals Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes

2010 ◽  
Vol 44 (4) ◽  
pp. 195-201 ◽  
Author(s):  
Samantha Gardner ◽  
Emmanouil Stavrou ◽  
Patricia E Rischitor ◽  
Elena Faccenda ◽  
Adam J Pawson
Keyword(s):  
Signal Transduction ◽  
Gnrh Receptor ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Key Players ◽  
Canonical Wnt ◽  
Recent Demonstration

The binding of GnRH to its receptor on pituitary gonadotropes leads to the targeting of a diverse array of signalling mediators. These mediators drive multiple signal transduction pathways, which in turn regulate a variety of cellular processes, including the biosynthesis and secretion of the gonadotropins LH and FSH. Advances in our understanding of the mechanisms and signalling pathways that are recruited to regulate gonadotrope function are continually being made. This review will focus on the recent demonstration that key mediators of the canonical Wnt signalling pathway are targeted by GnRH in gonadotropes, and that these may play essential roles in regulating the expression of many of the key players in gonadotrope biology, including the GnRH receptor and the gonadotropins.

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