scholarly journals Mechanisms Regulating Abnormal Circular RNA Biogenesis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4185
Author(s):  
Ying Huang ◽  
Qubo Zhu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Circular Rna ◽  
Regulatory Elements ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Closed Loops ◽  
Rna Biogenesis ◽  
Cis And Trans ◽  
Functional Mechanisms

Circular RNAs (circRNAs), which are a class of endogenous RNA with covalently closed loops, play important roles in epigenetic regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, how circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “back-splicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis and trans elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated how circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.

scholarly journals Circular RNAs in Cardiovascular Disease: An Overview

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ximin Fan ◽  
Xinyu Weng ◽  
Yifan Zhao ◽  
Wei Chen ◽  
Tianyi Gan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Noncoding Rna ◽  
Essential Role ◽  
Closed Loop ◽  
Regulation Of Gene Expression ◽  
Circular Rna ◽  
Circular Rnas ◽  
Mirna Sponges

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

Regulation of gene expression during spermatogenesis at transcriptional level

2011 ◽  
Vol 33 (12) ◽  
pp. 1300-1307
Author(s):  
Xiu-Jun ZHANG ◽  
Mei-Ling LIU ◽  
Meng-Chun JIA
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level

scholarly journals Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xuexiu Zhang ◽  
Jianning Yao ◽  
Haoling Shi ◽  
Bing Gao ◽  
Haining Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Sp1 Transcription Factor ◽  
Reporter Assays ◽  
Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

scholarly journals Regulation of proton-translocating V-ATPases.

1997 ◽  
Vol 200 (2) ◽  
pp. 225-235 ◽  
Author(s):  
H Merzendorfer ◽  
R Gräf ◽  
M Huss ◽  
W R Harvey ◽  
H Wieczorek
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Plasma Membranes ◽  
Regulation Of Gene Expression ◽  
Transcriptional Level ◽  
Structural Domains ◽  
Sh Groups ◽  
Signalling Molecules ◽  
Membrane Spanning ◽  
Regulation Of Enzyme Activity

Vacuolar-type ATPases (V-ATPases) are proton-translocating enzymes that occur in the endomembranes of all eukaryotes and in the plasma membranes of many eukaryotes. They are multisubunit, heteromeric proteins composed of two structural domains, a peripheral, catalytic V1 domain and a membrane-spanning V0 domain. Both the multitude of locations and the heteromultimeric structure make it likely that the expression and the activity of V-ATPases are regulated in various ways. Regulation of gene expression encompasses control of transcription as well as control at the post-transcriptional level. Regulation of enzyme activity encompasses many diverse mechanisms such as disassembly/reassembly of V1 and V0 domains, oxidation of SH groups, control by activator and inhibitor proteins or by small signalling molecules, and sorting of the holoenzyme or its subunits to target membranes.

scholarly journals Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1016 ◽  
Author(s):  
Claudia Dompe ◽  
Krzysztof Janowicz ◽  
Greg Hutchings ◽  
Lisa Moncrieff ◽  
Maurycy Jankowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cancer Therapy ◽  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Transcriptional Level ◽  
Cancer Therapies ◽  
Stem Cell Engineering ◽  
Anti Cancer

The epigenome denotes all the information related to gene expression that is not contained in the DNA sequence but rather results from chemical changes to histones and DNA. Epigenetic modifications act in a cooperative way towards the regulation of gene expression, working at the transcriptional or post-transcriptional level, and play a key role in the determination of phenotypic variations in cells containing the same genotype. Epigenetic modifications are important considerations in relation to anti-cancer therapy and regenerative/reconstructive medicine. Moreover, a range of clinical trials have been performed, exploiting the potential of epigenetics in stem cell engineering towards application in disease treatments and diagnostics. Epigenetic studies will most likely be the basis of future cancer therapies, as epigenetic modifications play major roles in tumour formation, malignancy and metastasis. In fact, a large number of currently designed or tested clinical approaches, based on compounds regulating epigenetic pathways in various types of tumours, employ these mechanisms in stem cell bioengineering.

Circular RNA as a potential diagnostic and/or therapeutic target for endometriosis

2020 ◽  
Vol 14 (13) ◽  
pp. 1277-1287
Author(s):  
Parisa M Dana ◽  
Mona Taghavipour ◽  
Hamed Mirzaei ◽  
Bahman Yousefi ◽  
Bahram Moazzami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Circular Rnas ◽  
Biological Functions ◽  
Parental Gene

Endometriosis is a pathology form of endometrium that behaves in a similar way to malignancies, such as invasion and resistance to apoptosis. Circular RNAs (CircRNAs) are a class of noncoding RNAs that have several biological functions including, miRNA sponging, sequestering of proteins, enhancing parental gene expression and translation resulting in polypeptides. In this review, we highlighted the roles of circRNAs as potential diagnostic and therapeutic biomarkers in endometriosis. Moreover, we summarized the roles of circRNAs in the pathogenesis of endometriosis via different signaling pathways, such as the miRNA network and apoptosis.

Factors Involved in the Regulation of Type I Collagen Gene Expression: Implication in Fibrosis

2002 ◽  
Vol 227 (5) ◽  
pp. 301-314 ◽  
Author(s):  
Asish K. Ghosh
Keyword(s):  
Gene Expression ◽  
Collagen Synthesis ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Regulatory Elements ◽  
Transcriptional Level ◽  
Type I ◽  
Collagen Gene ◽  
Cis Acting ◽  
Collagen Gene Expression

Type I collagen, the major component of extracellular matrix in skin and other tissues, is a heterotrimer of two α1 and one α2 collagen polypeptides. The synthesis of both chains is highly regulated by different cytokines at the transcriptional level. Excessive synthesis and deposition of collagen in the dermal region causes thick and hard skin, a clinical manifestation of scleroderma. To better understand the causes of scleroderma or other tissue fibrosis, it is very Important to investigate the molecular mechanisms that cause upregulation of the Type I collagen synthesis in these tissues. Several cis-acting regulatory elements and trans-acting protein factors, which are involved in basal as well as cytokine-modulated Type I collagen gene expression, have been identified and characterized. Hypertranscription of Type I collagen in scleroderma skin fibroblasts may be due to abnormal activities of different positive or negative transcription factors In response to different abnormally induced signaling pathways. In this review, I discuss the present day understanding about the involvement of different factors in the regulation of basal as well as cytokine-modulated Type I collagen gene expression and its implication in scleroderma research.

scholarly journals Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Jun Xu ◽  
Kaifeng Zhou ◽  
Chong Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Critical Role ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Expression Level ◽  
Circular Rnas ◽  
Competing Endogenous Rna ◽  
Potential Therapeutic Target

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

Identification of a Gain-of-Function SNP Causing a New Model of α-Thalassaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 523-523
Author(s):  
Marco De Gobbi ◽  
Vip Viprakasit ◽  
Pieter J. de Jong ◽  
Yuko Yoshinaga ◽  
Jan-Fang Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Globin Gene ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Regulatory Elements ◽  
Causative Mutation ◽  
Regulatory Sequences ◽  
Chromosome 16 ◽  
Upstream Regulatory Sequences

Abstract The human α globin cluster includes an embryonic gene ζ and 2 fetal/adult genes (α2 and α1) arranged along the chromosome in the order in which they are expressed in development (5′-ζ-pseudoζ- αD- α2-α1-𝛉-3′). Fully activated expression of these genes in erythroid cells depends on upstream regulatory elements of which HS-40, located 40kb upstream of the cluster, appears to exert the greatest effect. We have recently shown that during terminal differentiation, key transcription factors (GATA-2, GATA-1, NF-E2, SCL complex) sequentially bind the α promoters and their regulatory elements and a domain of histone acetylation develops which eventually encompasses the entire α globin cluster including the upstream regulatory sequences. α-thalassemia most frequently results from deletions or point mutations affecting the structural α globin genes, but may also result from rare sporadic deletions which remove the upstream regulatory sequences. In a single family α globin expression was silenced by a mutation which drives an anti-sense RNA through the α gene. Alpha thalassemia may also result from inherited and acquired mutations in a trans-acting factor called ATRX. Over the past few years we have continued to screen for new mechanisms which lead to α thalassemia and thereby elucidate new principles underlying the regulation of gene expression in hemopoiesis. Here we describe a new mechanism of α thalassemia occurring in Pacific Islanders in whom we could detect no mutations or rearrangements in the α globin gene locus. Despite this, extensive genetic analysis showed unequivocally that the causative mutation is linked to the terminal 169kb of chromosome 16 (Viprakasit et al accompanying abstract). Analysis of globin synthesis, steady state RNA levels and detection of RNA in situ demonstrated that the mutation downregulates α globin transcription. To identify the mutation, we constructed a new BAC library from an affected homozygote, isolated and re-sequenced the candidate region and focussed further analysis on 8 SNPS within the α globin cluster, one of which creates a new GATA-1 binding site (GACA>GATA). Using primary erythroblasts from normal individuals and patients with this form of thalassemia, together with interspecific hybrids containing either the normal or abnormal copy of chromosome 16, we have shown that this SNP creates a new binding site in vivo for GATA-1 and the SCL complex. Furthermore, the chromatin at this site becomes activated as judged by acetylation of histone H3 and H4 (H3ac2 and H4ac4) and methylation of histone H3 (H3K4me2). Based on these data we postulate that an active transcriptional complex binding this new GATA site created by the SNP-mutation, could distract the upstream regulatory regions, which normally interact with the α globin promoter, and silence α globin gene expression. This model thus represents a new example of α globin gene down-regulation and a new mechanism by which gene expression can be perturbed during hemopoiesis.

scholarly journals The Causes and Consequences of Spatial Organization of the Genome in Regulation of Gene Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Marios Agelopoulos ◽  
Spyros Foutadakis ◽  
Dimitris Thanos
Keyword(s):  
Gene Expression ◽  
Spatial Organization ◽  
Protein Complexes ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Current View ◽  
Regulation Of Expression ◽  
Time Space ◽  
Transcriptional Regulatory ◽  
Immune Related Genes

Regulation of gene expression in time, space and quantity is orchestrated by the functional interplay of cis-acting elements and trans-acting factors. Our current view postulates that transcription factors recognize enhancer DNA and read the transcriptional regulatory code by cooperative DNA binding to specific DNA motifs, thus instructing the recruitment of transcriptional regulatory complexes forming a plethora of higher-ordered multi-protein-DNA and protein-protein complexes. Here, we reviewed the formation of multi-dimensional chromatin assemblies implicated in gene expression with emphasis on the regulatory role of enhancer hubs as coordinators of stochastic gene expression. Enhancer hubs contain many interacting regulatory elements and represent a remarkably dynamic and heterogeneous network of multivalent interactions. A functional consequence of such complex interaction networks could be that individual enhancers function synergistically to ensure coordination, tight control and robustness in regulation of expression of spatially connected genes. In this review, we discuss fundamental paradigms of such inter- and intra- chromosomal associations both in the context of immune-related genes and beyond.

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