scholarly journals NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yanke Zhang ◽  
Guojun Chen ◽  
Baobing Gao ◽  
Yunlin Li ◽  
Shuli Liang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Seizure Activity ◽  
Surface Expression ◽  
Biological Processes ◽  
Onset Latency ◽  
Downstream Target ◽  
Group A ◽  
Patients With Epilepsy ◽  
The Relationship ◽  
Nuclear Receptor Subfamily

Abstract Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models. Moreover, reciprocal coimmunoprecipitation of NR4A1 and NR2B demonstrated their interaction. Furthermore, the expression of p-NR2B (Tyr1472) in epileptic mice and the expression of NR2B in the postsynaptic density (PSD) were significantly reduced in the lenti-shNR4A1 group, indicating that NR4A1 knockdown partly decreased surface NR2B by promoting NR2B internalization. These results are the first to indicate that the expression of NR4A1 in epileptic brain tissues may provide new insights into the molecular mechanisms underlying epilepsy.

scholarly journals The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity

2016 ◽  
Vol 18 ◽  
Author(s):  
Wei Wang ◽  
Xuefeng Wang ◽  
Lang Chen ◽  
Yujiao Zhang ◽  
Zucai Xu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Surface Expression ◽  
Camp Response Element Binding ◽  
Neuronal Firing ◽  
Luciferase Reporter ◽  
Onset Latency ◽  
Drug Induced ◽  
Rat Models ◽  
Patients With Epilepsy

miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3′UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.

scholarly journals Integrating Multiple Microarray Data for Cancer Pathway Analysis Using Bootstrapping K-S Test

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Bing Han ◽  
Xue-Wen Chen ◽  
Xinkun Wang ◽  
Elias K. Michaelis
Keyword(s):  
Microarray Data ◽  
Molecular Mechanisms ◽  
Large Set ◽  
Biological Processes ◽  
Different Types ◽  
Kolmogorov Smirnov ◽  
Integrative Method ◽  
The Relationship ◽  
Key Pathways ◽  
Smirnov Test

Previous applications of microarray technology for cancer research have mostly focused on identifying genes that are differentially expressed between a particular cancer and normal cells. In a biological system, genes perform different molecular functions and regulate various biological processes via interactions with other genes thus forming a variety of complex networks. Therefore, it is critical to understand the relationship (e.g., interactions) between genes across different types of cancer in order to gain insights into the molecular mechanisms of cancer. Here we propose an integrative method based on the bootstrapping Kolmogorov-Smirnov test and a large set of microarray data produced with various types of cancer to discover common molecular changes in cells from normal state to cancerous state. We evaluate our method using three key pathways related to cancer and demonstrate that it is capable of finding meaningful alterations in gene relations.

scholarly journals PPARGEpigenetic Deregulation and Its Role in Colorectal Tumorigenesis

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lina Sabatino ◽  
Alessandra Fucci ◽  
Massimo Pancione ◽  
Vittorio Colantuoni
Keyword(s):  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Epigenetic Modifications ◽  
Cancer Development ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Colorectal Tumorigenesis ◽  
Epigenetic Machinery ◽  
The Relationship

Peroxisome proliferator-activated receptor gamma (PPARγ) plays critical roles in lipid storage, glucose metabolism, energy homeostasis, adipocyte differentiation, inflammation, and cancer. Its function in colon carcinogenesis has largely been debated; accumulating evidence, however, supports a role as tumor suppressor through modulation of crucial pathways in cell differentiation, apoptosis, and metastatic dissemination. Epigenetics adds a further layer of complexity to gene regulation in several biological processes. In cancer, the relationship with epigenetic modifications has provided important insights into the underlying molecular mechanisms. These studies have highlighted how epigenetic modifications influencePPARGgene expression in colorectal tumorigenesis. In this paper, we take a comprehensive look at the current understanding of the relationship between PPARγand cancer development. The role that epigenetic mechanisms play is also addressed disclosing novel crosstalks betweenPPARGsignaling and the epigenetic machinery and suggesting how this dysregulation may contribute to colon cancer development.

A Test of Satiation as a Function of Adaptation in Stuttering

1969 ◽  
Vol 12 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Harold A. Peterson ◽  
Mary Beth Rieck ◽  
Rita K. Hoff
Keyword(s):  
Semantic Differential ◽  
Repeated Readings ◽  
Group A ◽  
Relationship Of ◽  
The Relationship

To test the relationship of adaptation and satiation as hypothesized by Jakobovits, satiation of meaning as a function of repeated readings for adaptation was measured in the performance of 14 male stutterers. The subjects as a group exhibited both satiation and adaptation, but the two phenomena did not occur simultaneously in a significant number of the members of the group. A reduction in meaningfulness, as measured by the semantic differential, was not shown to be a significant factor in the reduction of stuttering frequency for the individuals in the group. Satiation and adaptation were not established as the same phenomenon, although the two may still be related through another factor.

Appreciation of the importance of pregravid preparation and reproductive attitudes of women of childbearing age in the city of Omsk

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 48-52
Author(s):  
E N Kravchenko ◽  
R A Morgunov
Keyword(s):  
Women Of Childbearing Age ◽  
Childbearing Age ◽  
Pregnancy And Childbirth ◽  
Perinatal Center ◽  
History Of ◽  
Group A ◽  
Group B ◽  
Complicated Pregnancy ◽  
The Relationship ◽  
The City

The aim of the study. Assess the importance of pregravid preparation and outcomes of pregnancy and childbirth, depending on the reproductive attitudes of women in the city of Omsk. Materials and methods. The study included 92 women who were divided into groups: group A (n=43) - women whose pregnancy was planned; group B (n=49) - women whose pregnancy occurred accidentally. Each group was divided into subgroups depending on age: from 18 to 30 and from 31 to 49 years. For each patient included in the study, a specially designed map was filled out. These patients were interviewed at the City Clinical Perinatal Center. Results. Comparative analysis revealed the relationship between the reproductive settings of women of childbearing age and the peculiarity of the course of pregnancy and childbirth in these patients. Summary. The majority of women of fertile age are married: in subgroup AA - 25 (96.2%), AB - 13 (76.5%), BA - 25 (92.6%), BB - 20 (91.0%). The predominant number of women of fertile age have one or more abortions: in subgroup AA - 12 (46.2%), AB - 6 (35.3%), in subgroups of comparison BA - 8 (29.6%), BB - 6 (27.3%). More than half of the women of fertile age surveyed have a history of untreated cervical pathology (from 40.8% to 64.7%). The course of pregnancy in women planning pregnancy in most cases proceeded without complications: in subgroup AA - 13 (50.0%), AB - 11 (64.7%). The most common cause of complicated pregnancy in women whose pregnancy occurred accidentally is the threat of spontaneous miscarriage: in subgroup BA - 15 (55.6%), BB - 16 (72.7%). The uncomplicated course of labor more often [subgroup AA - 19 (73.0%), AB - 12 (70.6%)] was observed in women whose pregnancy was planned and they were motivated to give birth to a healthy child.

CASC15：A tumor-associated long non-coding RNA

2020 ◽  
Vol 26 ◽  
Author(s):  
Bei Wang ◽  
Wen Xu ◽  
Yuxuan Cai ◽  
Chong Guo ◽  
Gang Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Therapeutic Target ◽  
Cancer Colorectal ◽  
Tumor Development ◽  
Pathophysiological Mechanism ◽  
Biological Processes ◽  
Non Coding Rna ◽  
Cancer Côlon ◽  
The Relationship ◽  
Long Non Coding Rna

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarizes the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma, nasopharyngeal carcinoma. However, CASC15 has been found to be downexpressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Lisha Xie ◽  
Tao Jiang ◽  
Ailan Cheng ◽  
Ting Zhang ◽  
Pin Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Before And After

Background: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. Methods: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. Results: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. Conclusion: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

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