scholarly journals MicroRNA Era: The Importance for Diagnosis and Prognosis of Adrenocortical Tumors

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
João Evangelista Bezerra ◽  
Ana Claudia Latronico
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Essential Role ◽  
Pediatric Patients ◽  
Regulation Of Gene Expression ◽  
Adrenal Tumors ◽  
Expression Levels ◽  
Adrenocortical Tumors ◽  
Diagnosis And Prognosis ◽  
Current Review

MicroRNAs play an essential role in posttranscriptional regulation of gene expression. They are evolutionary conserved, small, noncoding, 19–22-nucleotide RNAs, whose abnormalities, such as up- or downregulated expression, have been associated with several neoplasms, including adrenocortical tumors. Expression levels of distinct microRNAs can distinguish benign from malignant adrenal tumors. This current review provides recent data on the miRNAs profile in benign and malignant adrenocortical tumors diagnosed in adult and pediatric patients.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

scholarly journals Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Mapk Pathway ◽  
Alveolar Epithelial Cell ◽  
Marker Gene ◽  
Regulation Of Gene Expression ◽  
Surfactant Protein ◽  
Specific Gene ◽  
Expression Levels ◽  
Alveolar Epithelial

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

scholarly journals Differential Expression of MicroRNAs between Eutopic and Ectopic Endometrium in Ovarian Endometriosis

2010 ◽  
Vol 2010 ◽  
pp. 1-29 ◽  
Author(s):  
Nicoletta Filigheddu ◽  
Ilaria Gregnanin ◽  
Paolo E. Porporato ◽  
Daniela Surico ◽  
Beatrice Perego ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Differentially Expressed ◽  
Ovarian Endometriosis ◽  
Eutopic Endometrium ◽  
Ectopic Endometrium

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identifiedin silicotheir predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopicversuseutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

scholarly journals Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development

2009 ◽  
Vol 106 (17) ◽  
pp. 7028-7033 ◽  
Author(s):  
Zhe Ji ◽  
Ju Youn Lee ◽  
Zhenhua Pan ◽  
Bingjun Jiang ◽  
Bin Tian
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Alternative Polyadenylation ◽  
Untranslated Regions ◽  
C2c12 Myoblast ◽  
Control Of Gene Expression ◽  
Differentiation And Proliferation

The 3′ untranslated regions (3′ UTRs) of mRNAs containcis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3′ UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3′ UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3′ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.

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.

scholarly journals Multivariable regulation of gene expression plasticity in metazoans

2019 ◽  
Author(s):  
Long Xiao ◽  
Zhiguang Zhao ◽  
Fei He ◽  
Zhuo Du
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Rapid Change ◽  
High Plasticity ◽  
Expression Levels ◽  
Genome Wide ◽  
Expression Potential ◽  
Highly Correlated

ABSTRACTAn important capacity of genes is the rapid change of expression levels to cope with environment, known as expression plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness, and adaptation. In this study, we systematically quantified genome-wide gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studies features including gene expression potential and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promoter cis-elements, trans-acting factors (such as CFCF), and gene body histone modifications (H3K36me3, H3K79me2, and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals general properties, physiological implications, and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.

scholarly journals Crystal structure of a Y-box binding protein 1 (YB-1)–RNA complex reveals key features and residues interacting with RNA

2019 ◽  
Vol 294 (28) ◽  
pp. 10998-11010 ◽  
Author(s):  
Xiao-Juan Yang ◽  
Hong Zhu ◽  
Shi-Rong Mu ◽  
Wen-Juan Wei ◽  
Xun Yuan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Regulation Of Gene Expression ◽  
Binding Activity ◽  
Core Motif ◽  
Variable Exon ◽  
Nucleotide Resolution

The Y-box binding protein 1 (YB-1) is a member of the cold shock domain (CSD) protein family and is recognized as an oncogenic factor in several solid tumors. By binding to RNA, YB-1 participates in several steps of posttranscriptional regulation of gene expression, including mRNA splicing, stability, and translation; microRNA processing; and stress granule assembly. However, the mechanisms in YB-1–mediated regulation of RNAs are unclear. Previously, we used both systematic evolution of ligands by exponential enrichment (SELEX) and individual-nucleotide resolution UV cross-linking and immunoprecipitation coupled RNA-Seq (iCLIP-Seq) analyses, which defined the RNA-binding consensus sequence of YB-1 as CA(U/C)C. We also reported that through binding to its core motif CAUC in primary transcripts, YB-1 regulates the alternative splicing of a CD44 variable exon and the biogenesis of miR-29b-2 during both Drosha and Dicer steps. To elucidate the molecular basis of the YB-1–RNA interactions, we report high-resolution crystal structures of the YB-1 CSD in complex with different RNA oligos at 1.7 Å resolution. The structure revealed that CSD interacts with RNA mainly through π–π stacking interactions assembled by four highly conserved aromatic residues. Interestingly, YB-1 CSD forms a homodimer in solution, and we observed that two residues, Tyr-99 and Asp-105, at the dimer interface are important for YB-1 CSD dimerization. Substituting these two residues with Ala reduced CSD's RNA-binding activity and abrogated the splicing activation of YB-1 targets. The YB-1 CSD–RNA structures presented here at atomic resolution provide mechanistic insights into gene expression regulated by CSD-containing proteins.

Different early-signaling pathways coupled to transcriptional and posttranscriptional regulation of gene expression during mitogenic activation of T lymphocytes

1987 ◽  
Vol 7 (8) ◽  
pp. 3004-3007
Author(s):  
M W White ◽  
A K Oberhauser ◽  
C A Kuepfer ◽  
D R Morris
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Alpha Tubulin ◽  
Kinase C

Two categories of mitogen-induced mRNAs were defined in T lymphocytes. The type 1 messages (represented by c-myc) were regulated transcriptionally, and their expression seemed to be calmodulin dependent. The type 2 messages (ornithine decarboxylase, actin, and alpha-tubulin) were regulated posttranscriptionally through activation of protein kinase C.

scholarly journals TIS11 Family Proteins and Their Roles in Posttranscriptional Gene Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-11 ◽  
Author(s):  
Maria Baou ◽  
Andrew Jewell ◽  
John J. Murphy
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Present Review ◽  
Untranslated Regions ◽  
Cell Functions ◽  
Small Family ◽  
The Past ◽  
Posttranscriptional Gene Regulation

Posttranscriptional regulation of gene expression of mRNAs containing adenine-uridine rich elements (AREs) in their untranslated regions is mediated by a number of different proteins that interact with these elements to either stabilise or destabilise them. The present review concerns the TPA-inducible sequence 11 (TIS11) protein family, a small family of proteins, that appears to interact with ARE-containing mRNAs and promote their degradation. This family of proteins has been extensively studied in the past decade. Studies have focussed on determining their biochemical functions, identifying their target mRNAs, and determining their roles in cell functions and diseases.

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