Prospects for miR-21 as a Target in the Treatment of Lung Diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Yan Ding ◽  
Yapeng Hou ◽  
Yanhong Liu ◽  
Xiaoyong Xie ◽  
Yong Cui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Diseases ◽  
Target Gene ◽  
Molecular Therapy ◽  
Signaling Cascade ◽  
Transcriptional Level ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth ◽  
Non Coding Rna ◽  
Evolutionarily Conserved

: MicroRNA (miRNA/miR) is a class of small evolutionarily conserved non-coding RNA, which can inhibit the target gene expression at post-transcriptional level and serve as significant roles in cell differentiation, proliferation, migration and apoptosis. Of note, the aberrant miR-21 has been involved in the generation and development of multiple lung diseases, and identified as a candidate of biomarker, therapeutic target, or indicator of prognosis. MiR-21 relieves acute lung injury via depressing the PTEN/Foxo1-TLR4/NF-κB signaling cascade,where as promotes lung cancer cell growth, metastasis, and chemo/radio-resistance by decreasing the expression of PTEN and PDCD4 and promoting the PI3K/AKT transduction.The purpose of this review is to elucidate the potential mechanisms of miR-21 associated lung diseases, with an emphasis on its dual regulating effects, which will trigger novel paradigms in the molecular therapy.

scholarly journals Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4034-4046 ◽  
Author(s):  
Giuseppe Zardo ◽  
Alberto Ciolfi ◽  
Laura Vian ◽  
Linda M. Starnes ◽  
Monia Billi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcriptional Control ◽  
Transcriptional Level ◽  
Seed Region ◽  
Mrna Targets ◽  
Epigenetic Events ◽  
Evolutionarily Conserved ◽  
Lineage Decision ◽  
Chromatin Remodeling Complexes

Abstract Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin “bivalent domains,” hypermethylation, recruitment of polycomb (PcG)–RNAi complexes, and miR-223 promoter targeting activity. During granulopoiesis, miR-223 localizes inside the nucleus and targets the NFI-A promoter region containing PcGs binding sites and miR-223 complementary DNA sequences, evolutionarily conserved in mammalians. Remarkably, both the integrity of the PcGs-RNAi complex and DNA sequences matching the seed region of miR-223 are required to induce NFI-A transcriptional silencing. Moreover, ectopic miR-223 expression in human myeloid progenitors causes heterochromatic repression of NFI-A gene and channels granulopoiesis, whereas its stable knockdown produces the opposite effects. Our findings indicate that, besides the regulation of translation of mRNA targets, endogenous miRs can affect gene expression at the transcriptional level, functioning in a critical interface between chromatin remodeling complexes and the genome to direct fate lineage determination of hematopoietic progenitors.

scholarly journals The role of vitamins and minerals in modulating the expression of microRNA

2014 ◽  
Vol 27 (1) ◽  
pp. 94-106 ◽  
Author(s):  
Emma L. Beckett ◽  
Zoe Yates ◽  
Martin Veysey ◽  
Konsta Duesing ◽  
Mark Lucock
Keyword(s):  
Gene Expression ◽  
Food Sources ◽  
Transcriptional Level ◽  
Disease States ◽  
Regulatory Circuit ◽  
Non Coding Rna ◽  
Epigenetic Machinery ◽  
Health And Disease ◽  
Expression Potential

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

scholarly journals Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling

2015 ◽  
Vol 35 (19) ◽  
pp. 3301-3311 ◽  
Author(s):  
Jiandang Shi ◽  
Yajuan Liu ◽  
Xuehe Xu ◽  
Wen Zhang ◽  
Tianxin Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Target Gene ◽  
Central Question ◽  
Cancer Cell Growth ◽  
Positive Role ◽  
Content Type

Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination. Inactivation of USP47 by RNAi increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. Furthermore, USP47 deubiquitinates itself, whereas β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47. Finally,in vivostudies in theDrosophilawing suggest that UBP64E, the USP47 counterpart inDrosophila, is required for Armadillo stabilization and plays a positive role in regulating Wnt target gene expression.

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 Identification and Evaluation of Reference Genes for Normalization of Gene Expression in Developmental Stages, Sexes, and Tissues of Diaphania caesalis (Lepidoptera, Pyralidae)

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zheng Wang ◽  
Qianqian Meng ◽  
Xi Zhu ◽  
Shiwei Sun ◽  
Aiqin Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Target Gene ◽  
Target Genes ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Transcriptional Level ◽  
Internal Reference ◽  
Target Gene Expression ◽  
Qrt Pcr

Abstract Diaphania caesalis (Walker) is an important boring insect mainly distributed in subtropical and tropical areas and attacked tropical woody grain crops, such as starchy plants of Artocarpus. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful approach for investigating target genes expression profiles at the transcriptional level. However, the identification and selection of internal reference genes, which is often overlooked, is the most vital step before the analysis of target gene expression by qRT-PCR. So far, the reliable internal reference genes under a certain condition of D. caesalis have not been investigated. Therefore, this study evaluated the expression stability of eight candidate reference genes including ACT, β-TUB, GAPDH, G6PDH, RPS3a, RPL13a, EF1α, and EIF4A in different developmental stages, tissues and sexes using geNorm, NormFinder and BestKeeper algorithms. To verify the stability of the recommended internal reference genes, the expression levels of DcaeOBP5 were analyzed under different treatment conditions. The results indicated that ACT, RPL13a, β-TUB, RPS3a, and EF1α were identified as the most stable reference genes for further studies on target gene expression involving different developmental stages of D. caesalis. And ACT and EIF4A were recommended as stable reference genes for different tissues. Furthermore, ACT, EF1α, and RPS3a were ranked as the best reference genes in different sexes based on three algorithms. Our research represents the critical first step to normalize qRT-PCR data and ensure the accuracy of expression of target genes involved in phylogenetic and physiological mechanism at the transcriptional level in D. caesalia.

Long non-coding RNA EPIC1 promotes human lung cancer cell growth

2018 ◽  
Vol 503 (3) ◽  
pp. 1342-1348 ◽  
Author(s):  
Bing Zhang ◽  
Hui-Yu Lu ◽  
Yun-Hong Xia ◽  
Ai-Gui Jiang ◽  
Yu-Xin Lv
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth ◽  
Human Lung Cancer Cell ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease

2021 ◽  
Vol 11 (4) ◽  
pp. 230-254
Author(s):  
Federica Amodio ◽  
Martina Caiazza ◽  
Fabio Fimiani ◽  
Paolo Calabrò ◽  
Giuseppe Limongelli
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Cell Communication ◽  
Transcriptional Level ◽  
Negative Regulators ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
New Perspective ◽  
Therapeutic Tools ◽  
The Stability

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).

scholarly journals Atrophin–Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR

2013 ◽  
Vol 203 (4) ◽  
pp. 575-583 ◽  
Author(s):  
Zhao Zhang ◽  
Jing Feng ◽  
Chenyu Pan ◽  
Xiangdong Lv ◽  
Wenqing Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Hedgehog Signaling ◽  
Target Gene ◽  
Cubitus Interruptus ◽  
C Terminus ◽  
Evolutionarily Conserved ◽  
N Terminus ◽  
Hh Signaling

The evolutionarily conserved Hedgehog (Hh) signaling pathway is transduced by the Cubitus interruptus (Ci)/Gli family of transcription factors that exist in two distinct repressor (CiR/GliR) and activator (CiA/GliA) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which CiR/GliR properly represses target gene expression is poorly understood. Here, we used Drosophila melanogaster and zebrafish models to define a repressor function of Atrophin (Atro) in Hh signaling. Atro directly bound to Ci through its C terminus. The N terminus of Atro interacted with a histone deacetylase, Rpd3, to recruit it to a Ci-binding site at the decapentaplegic (dpp) locus and reduce dpp transcription through histone acetylation regulation. The repressor function of Atro in Hh signaling was dependent on Ci. Furthermore, Rerea, a homologue of Atro in zebrafish, repressed the expression of Hh-responsive genes. We propose that the Atro–Rpd3 complex plays a conserved role to function as a CiR corepressor.

scholarly journals Evolutionarily Conserved Long Non-coding RNA Regulates Gene Expression in Cytokine Storm During COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Olanrewaju B. Morenikeji ◽  
Kahleel Bernard ◽  
Ellis Strutton ◽  
Madeleine Wallace ◽  
Bolaji N. Thomas
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Regulatory Elements ◽  
Cytokine Storm ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Evolutionarily Conserved ◽  
Multiple Species

Coronavirus is a family of viruses including alpha-, beta-, gamma-, delta-coronaviruses. Only alpha- and betacoronaviruses have been observed to infect humans. Past outbreaks of SARS-CoV and MERS-CoV, both betacoronavirus, are the result of a spillover from animals. Recently, a new strain termed SARS-CoV-2 emerged in December 2019 in Wuhan, China. Severe cases of COVID-19, the disease caused by SARS-CoV-2, lead to acute respiratory distress syndrome (ARDS). One contributor to the development of ARDS is cytokine storm, an overwhelming inflammatory immune response. Long non-coding RNAs (lncRNAs) are genetic regulatory elements that, among many functions, alter gene expression and cellular processes. lncRNAs identified to be pertinent in COVID-19 cytokine storm have the potential to serve as disease markers or drug targets. This project aims to computationally identify conserved lncRNAs potentially regulating gene expression in cytokine storm during COVID-19. We found 22 lncRNAs that can target 10 cytokines overexpressed in COVID-19 cytokine storm, 8 of which targeted two or more cytokine storm cytokines. In particular, the lncRNA non-coding RNA activated by DNA damage (NORAD), targeted five out of the ten identified cytokine storm cytokines, and is evolutionarily conserved across multiple species. These lncRNAs are ideal candidates for further in vitro and in vivo analysis.

Sign in / Sign up

Export Citation Format

Share Document