scholarly journals From miRNA target gene network to miRNA function: miR-375 might regulate apoptosis and actin dynamics in the heart muscle via Rho-GTPases-dependent pathways

2020 ◽  
Author(s):  
German Osmak ◽  
Ivan Kiselev ◽  
Natalia Baulina ◽  
Olga Favorova
Keyword(s):  
Rho Gtpases ◽  
Heart Muscle ◽  
Target Genes ◽  
Heart Diseases ◽  
Specific Interaction ◽  
Actin Dynamics ◽  
Rna Molecules ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation

AbstractMicroRNAs (miRNAs) are short single-stranded non-coding RNA molecules, which are involved in regulation of main biological processes, such as apoptosis, cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases and data on its function in myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signalling pathways.We implemented our algorithm for miRNA function prediction into Python module, which is available at GitHub (https://github.com/GJOsmak/miRNET)

scholarly journals From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways

2020 ◽  
Vol 21 (24) ◽  
pp. 9670
Author(s):  
German Osmak ◽  
Ivan Kiselev ◽  
Natalia Baulina ◽  
Olga Favorova
Keyword(s):  
Rho Gtpases ◽  
Heart Muscle ◽  
Target Genes ◽  
Heart Diseases ◽  
Specific Interaction ◽  
Actin Dynamics ◽  
Rna Molecules ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, which are involved in the regulation of main biological processes, such as apoptosis or cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study, we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases, and data on its function in the myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signaling pathways. We implemented our algorithm for miRNA function prediction into a Python module, which is available at GitHub.

MicroRNA Determines the Fate of Intestinal Epithelial Cell Differentiation and Regulates Intestinal Diseases

2019 ◽  
Vol 20 (7) ◽  
pp. 666-673 ◽  
Author(s):  
Sujuan Ding ◽  
Gang Liu ◽  
Hongmei Jiang ◽  
Jun Fang
Keyword(s):  
Target Genes ◽  
Gastrointestinal Disease ◽  
Intestinal Barrier ◽  
Vital Role ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Intestinal Function ◽  
Cell Fates ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.

scholarly journals Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3485
Author(s):  
Assunta Sellitto ◽  
Giovanni Pecoraro ◽  
Giorgio Giurato ◽  
Giovanni Nassa ◽  
Francesca Rizzo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Metabolic Alterations ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Additional Level

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

scholarly journals Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fulu Dong ◽  
Yuan Zhang ◽  
Fei Xia ◽  
Yi Yang ◽  
Sidong Xiong ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Normal Pregnancy ◽  
Recurrent Spontaneous Abortion ◽  
Future Research ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

Hedgehog signals regulate multiple aspects of gastrointestinal development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2763-2772 ◽  
Author(s):  
M. Ramalho-Santos ◽  
D.A. Melton ◽  
A.P. McMahon
Keyword(s):  
Gastrointestinal Tract ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Critical Role ◽  
Indian Hedgehog ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mesodermal Origin ◽  
Gut Endoderm

The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.

scholarly journals Functional Analysis of Three miRNAs in Agropyron mongolicum Keng under Drought Stress

Agronomy ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 661 ◽  
Author(s):  
Xuting Zhang ◽  
Bobo Fan ◽  
Zhuo Yu ◽  
Lizhen Nie ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Northern China ◽  
Bioinformatic Analysis ◽  
Pcr Analysis ◽  
Rna Molecules ◽  
Natural Pasture ◽  
Non Coding Rna

Agropyron mongolicum Keng, a perennial diploid grass with high drought tolerance, belongs to the genus Agropyron, tribe Triticeae. It has made tremendous contributions toward reseeding natural pasture and seeding artificial grassland in China, especially in the arid and semi-arid area of northern China. As a wild relative of wheat, A. mongolicum is also a valuable resource for the genetic improvement of wheat crops. MicroRNAs are small non-coding RNA molecules ubiquitous in plants, which have been involved in responses to a wide variety of stresses including drought, salinity, chilling temperature. To date, little research has been done on drought-responsive miRNAs in A. mongolicum. In this study, two miRNA libraries of A. mongolicum under drought and normal conditions were constructed, and drought-responsive miRNAs were screened via Solexa high throughput sequencing and bioinformatic analysis. A total of 114 new miRNAs were identified in A. mongolicum including 53 conservative and 61 unconservative miRNAs, and 1393 target genes of 98 miRNAs were predicted. Seventeen miRNAs were found to be differentially expressed under drought stress, seven (amo-miR21, amo-miR62, amo-miR82, amo-miR5, amo-miR77, amo-miR44 and amo-miR17) of which were predicted to target on genes involved in drought tolerance. QRT-PCR analysis confirmed the expression changes of the seven drought related miRNAs in A. mongolicum. We then transformed the seven miRNAs into Arabidopsis thaliana plants, and three of them (amo-miR21, amo-miR5 and amo-miR62) were genetically stable. The three miRNAs demonstrated the same expression pattern in A. thaliana as that in A. mongolicum under drought stress. Findings from this study will better our understanding of the molecular mechanism of miRNAs in drought tolerance and promote molecular breeding of forage grass with improved adaption to drought.

scholarly journals Maximal Induction of a Subset of Interferon Target Genes Requires the Chromatin-Remodeling Activity of the BAF Complex

2002 ◽  
Vol 22 (18) ◽  
pp. 6471-6479 ◽  
Author(s):  
Hong Liu ◽  
Hyeog Kang ◽  
Rui Liu ◽  
Xin Chen ◽  
Keji Zhao
Keyword(s):  
Chromatin Remodeling ◽  
Target Genes ◽  
Transcription Activator ◽  
Baf Complex ◽  
Antiproliferative Effects ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Maximal Induction ◽  
Antiproliferative Activities

ABSTRACT The mammalian SWI/SNF-like chromatin-remodeling BAF complex plays several important roles in controlling cell proliferation and differentiation. Interferons (IFNs) are key mediators of cellular antiviral and antiproliferative activities. In this report, we demonstrate that the BAF complex is required for the maximal induction of a subset of IFN target genes by alpha IFN (IFN-α). The BAF complex is constitutively associated with the IFITM3 promoter in vivo and facilitates the chromatin remodeling of the promoter upon IFN-α induction. Furthermore, we show that the ubiquitous transcription activator Sp1 interacts with the BAF complex in vivo and augments the BAF-mediated activation of the IFITM3 promoter. Sp1 binds constitutively to the IFITM3 promoter in the absence of the BAF complex, suggesting that it may recruit and/or stabilize the BAF complex binding to the IFITM3 promoter. Our results bring new mechanistic insights into the antiproliferative effects of the chromatin-remodeling BAF complex.

scholarly journals Bio Immune(G)ene Medicine and the Use of miRNAs to Regulate the Cell

2018 ◽  
Vol 1 (2) ◽  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Allergic Diseases ◽  
Degradation Process ◽  
Transcriptional Level ◽  
Collateral Damage ◽  
Rna Molecules ◽  
The Past ◽  
Needed Information ◽  
Non Coding Rna

MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.

scholarly journals Myc stimulates B lymphocyte differentiation and amplifies calcium signaling

2007 ◽  
Vol 179 (4) ◽  
pp. 717-731 ◽  
Author(s):  
Tania Habib ◽  
Heon Park ◽  
Mark Tsang ◽  
Ignacio Moreno de Alborán ◽  
Andrea Nicks ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Target Genes ◽  
B Lymphocyte ◽  
Nuclear Translocation ◽  
Efflux Pump ◽  
Double Knockout ◽  
Activated T Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Deregulated expression of the Myc family of transcription factors (c-, N-, and L-myc) contributes to the development of many cancers by a mechanism believed to involve the stimulation of cell proliferation and inhibition of differentiation. However, using B cell–specific c-/N-myc double-knockout mice and Eμ-myc transgenic mice bred onto genetic backgrounds (recombinase-activating gene 2−/− and Btk−/− Tec−/−) whereby B cell development is arrested, we show that Myc is necessary to stimulate both proliferation and differentiation in primary B cells. Moreover, Myc expression results in sustained increases in intracellular Ca2+ ([Ca2+]i), which is required for Myc to stimulate B cell proliferation and differentiation. The increase in [Ca2+]i correlates with constitutive nuclear factor of activated T cells (NFAT) nuclear translocation, reduced Ca2+ efflux, and decreased expression of the plasma membrane Ca2+–adenosine triphosphatase (PMCA) efflux pump. Our findings demonstrate a revised model whereby Myc promotes both proliferation and differentiation, in part by a remarkable mechanism whereby Myc amplifies Ca2+ signals, thereby enabling the concurrent expression of Myc- and Ca2+-regulated target genes.

Sign in / Sign up

Export Citation Format

Share Document