scholarly journals Ameliorative Effects of Transcription Factor Dfoxo Over-Expression in a Drosophila Cardiovascular Disease Model

2020 ◽  
Vol 118 (3) ◽  
pp. 453a
Author(s):  
Marissa Sumathipala ◽  
Meera C. Viswanathan ◽  
Anna C. Blice-Baum
2020 ◽  
Author(s):  
Zhen-xian Lew ◽  
Hui-min Zhou ◽  
Yuan-yuan Fang ◽  
Zhen Ye ◽  
Wa Zhong ◽  
...  

Abstract Background: Transgelin, an actin-binding protein, is associated with the cytoskeleton remodeling. Our previous studies found that transgelin was up-regulated in node-positive colorectal cancer versus in node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms that transgelin participates in the metastasis of colon cancer cells.Methods: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of the endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequent high performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins potentially interacting with transgelin. Bioinformatics methods were used to analyze the 256 downstream transcripts regulated by transgelin to discriminate the specific key genes and signaling pathways. By analyzing the promoter region of these key genes, GCBI tools were used to predict the potential transcription factor(s) for these genes. The predicted transcription factors were matching to the proteins that have been identified to potentially interact with transgelin. The interaction between transgelin and these transcription factors was verified by co-immunoprecipitation and immunoblotting.Results: Transgelin was found to localize both in the cytoplasm and the nucleus of colon cancer cells. 297 proteins have been identified to interact with transgelin by co-immunoprecipitation and subsequent high performance liquid chromatography/mass spectrometry. Over-expression of TAGLN could lead to differential expression of 184 downstream genes. By constructing the network of gene-encoded proteins, 7 genes (CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1) have been discriminated as key genes using network topology analysis. They are mostly involved in the Rho signaling pathway. Poly ADP-ribose polymerase-1 (PARP1) was predicted as the unique transcription factor for the key genes and concurrently matching to the DNA-binding proteins potentially interacting with transgelin. Immunoprecipitation validated that PARP1 interacted with transgelin in human RKO colon cancer cells.Conclusions: The results of this study suggest that transgelin binds to PARP1 and regulates the expression of the downstream key genes mainly involving Rho signaling pathway, thus participates in the metastasis of colon cancer.


2015 ◽  
Vol 95 ◽  
pp. 26-34 ◽  
Author(s):  
Peiling Li ◽  
Aiping Song ◽  
Chunyan Gao ◽  
Jiafu Jiang ◽  
Sumei Chen ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S90-S90
Author(s):  
Zheng Kuai ◽  
Meiting Chen ◽  
yang yu ◽  
Fan Yang ◽  
chunxiang Zhang

Abstract Aging is the inevitable, irreversible decline in function on the cellular and organ level leading to increased incidence of the most frequent diseases such as cancer and cardiovascular disease, that occurs over time. whereas the molecular mechanisms of senescence remain largely unknown. Here we identified that a novel long noncoding RNA, Morrbid was significantly decreased in different organs of aged mice, such as heart, liver, spleen, lung, kidney and brain. Interestingly, the telomeres length of Morrbid KO mice were significantly shorted than the WT mice at the same age. We also found that Morrbid was steeply decreased in a natural mouse cardiac myocyte senescence model. The senescence of mouse cardiac myocytes was effectively attenuated by Morrbid over-expression shown by the decreased β-galactosidase staining, increased telomere activity, decreased production of ROS and decreased cell apoptosis, but was enhanced by Morrbid knockdown. The results suggest that Morrbid is a critical regulator in senescence and could be used as a novel diagnostic biomarker for it, and a new therapeutic target for diverse diseases.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1277 ◽  
Author(s):  
Kaur ◽  
Rawal ◽  
Siddiqui ◽  
Rohilla ◽  
Sharma ◽  
...  

Given the important role of angiogenesis in liver pathology, the current study investigated the role of Runt-related transcription factor 1 (RUNX1), a regulator of developmental angiogenesis, in the pathogenesis of non-alcoholic steatohepatitis (NASH). Quantitative RT-PCRs and a transcription factor analysis of angiogenesis-associated differentially expressed genes in liver tissues of healthy controls, patients with steatosis and NASH, indicated a potential role of RUNX1 in NASH. The gene expression of RUNX1 was correlated with histopathological attributes of patients. The protein expression of RUNX1 in liver was studied by immunohistochemistry. To explore the underlying mechanisms, in vitro studies using RUNX1 siRNA and overexpression plasmids were performed in endothelial cells (ECs). RUNX1 expression was significantly correlated with inflammation, fibrosis and NASH activity score in NASH patients. Its expression was conspicuous in liver non-parenchymal cells. In vitro, factors from steatotic hepatocytes and/or VEGF or TGF- significantly induced the expression of RUNX1 in ECs. RUNX1 regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of RUNX1. Furthermore, RUNX1 increased the angiogenic activity of ECs. This study reports that steatosis-induced RUNX1 augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH.


2018 ◽  
Vol 4 (2) ◽  
pp. 65-72 ◽  
Author(s):  
Roxana Buzas ◽  
Alexandru Florin Rogobete ◽  
Sonia Elena Popovici ◽  
Tudor Mateescu ◽  
Teodora Hoinoiu ◽  
...  

Abstract Worldwide, cardiovascular diseases (CVDs) represent one of the main causes of morbidity and mortality, and acute coronary syndromes are responsible for a large number of sudden cardiac deaths. One of the main challenges that still exist in this area is represented by the early detection and targeted monitoring of the pathophysiology involved in CVDs. During the last couple of years, researchers have highlighted the importance of molecular and epigenetic mechanisms involved in the initiation and augmentation of CVDs, culminating in their most severe form represented by acute myocardial infarction. One of the most studied molecular factors involved in this type of pathology is represented by nuclear transcription factor kappa B (NF-κB), as well as the involvement of microRNAs (miRNAs). It has been suggested that miRNAs can also be involved in the complex process of atheromatous plaque vulnerabilization that leads to an acute cardiac event. In this review paper, we describe the most important molecular mechanisms involved in the pathogenesis of CVDs and atheromatous plaque progression and vulnerabilization, which include molecular mechanisms dependent on NF-κB. For this paper, we used international databases (PubMed and Scopus). The keywords used for the search were “miRNAs biomarkers”, “miRNAs in cardiovascular disease”, “NF-κB in cardiovascular disease”, “molecular mechanism in cardiovascular disease”, and “myocardial NF-κB mechanisms”. Numerous molecular reactions that have NF-κB as a trigger are involved in the pathogenesis of CVDs. Moreover, miRNAs play an important role in initiating and aggravating certain segments of CVDs. Therefore, miRNAs can be used as biomarkers for early evaluation of CVDs. Furthermore, in the future, miRNAs could be used as a targeted molecular therapy in order to block certain mechanisms responsible for inducing CVDs and leading to acute cardiovascular events.


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