scholarly journals The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 202
Author(s):  
Ismael Riquelme ◽  
Pablo Pérez-Moreno ◽  
Pablo Letelier ◽  
Priscilla Brebi ◽  
Juan Carlos Roa
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Molecular Characteristics ◽  
Clinical Markers ◽  
Rna Transcripts ◽  
Gi Cancers ◽  
Tumor Types ◽  
Cumulative Evidence

Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways’ deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers.

scholarly journals The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4210-4218 ◽  
Author(s):  
Guibin Chen ◽  
Weihua Zeng ◽  
Akira Miyazato ◽  
Eric Billings ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Small Sample ◽  
Hematopoietic Progenitor Cell ◽  
Molecular Characteristics ◽  
Hematopoietic Progenitor ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yun Tang ◽  
Xiaobo Yang ◽  
Huaqing Shu ◽  
Yuan Yu ◽  
Shangwen Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Blood Samples ◽  
Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

scholarly journals Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

2019 ◽  
Vol 39 (01) ◽  
pp. 026-042 ◽  
Author(s):  
Yoon Yang ◽  
So Kim ◽  
Ekihiro Seki
Keyword(s):  
Adaptive Immunity ◽  
Molecular Mechanisms ◽  
Immune Surveillance ◽  
Therapeutic Targets ◽  
Nonalcoholic Fatty Liver ◽  
Adaptive Immune Cells ◽  
Early Hcc ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Factor Α

AbstractHepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a “premetastasis niche” in the liver.

The importance of epigenome research in the diagnosis and treatment of endometriosis

2018 ◽  
Vol 86 (4) ◽  
pp. 325
Author(s):  
Przemysław Krzysztof Wirstlein ◽  
Paweł P. Jagodziński ◽  
Małgorzata Szczepańska
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Diagnosis And Treatment ◽  
Control Of Gene Expression ◽  
Epigenetic Control ◽  
Current State

The causes of endometriosis remain unexplained. Studying the molecular mechanisms at the origin of the lesions leads to conclusions about the important role of the epigenome. This mini-review is a summary of the current state of knowledge about the processes of epigenetic control of gene expression involved in the pathogenesis of endometriosis.

scholarly journals Epigenetic Influences on Plant Responses to the Environment [University of Wisconsin - Oshkosh]

2019 ◽  
Author(s):  
Angela L Vickman ◽  
Travis Smith ◽  
Hayley Vandenboom ◽  
Lisa A. Dorn
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Physical Structure ◽  
Plant Responses ◽  
Appropriate Behavior ◽  
Stressful Environment ◽  
University Of Wisconsin

Plants and animals may respond to changes in the environment at the molecular level by changing the amount of a gene product (a protein) to generate the appropriate behavior or physical structure (a phenotype) for that environment. For example, an extremely stressful environment can cause plants to reproduce immediately rather than waiting for conditions to improve. The molecular mechanisms for changing phenotype with environment (phenotypic plasticity) are not clear, however previous studies have shown plasticity may be the result of failing to change expression to maintain a phenotype or a deliberate change in expression altering the phenotype. To explore the molecular mechanisms underlying phenotypic plasticity, I am using a minION sequencing apparatus to re-sequence three inbred lines of Arabidopsis thaliana with extreme phenotypic plasticity differences and gene expression differences with the environment. I will specifically explore the role of methylated cytosines and adenines in gene expression.

scholarly journals Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis

2020 ◽  
Author(s):  
Yumei Li ◽  
Bifei Li ◽  
Fan Chen ◽  
Weiyu Shen ◽  
Vladimir L. Katanaev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metastatic Melanoma ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Receptor Interaction ◽  
Melanoma Metastasis ◽  
Hub Genes ◽  
Core Genes

Abstract Background Metastasis is the leading cause of melanoma mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen for the key core genes and molecular mechanisms related to the metastasis of melanoma. Methods Gene expression profile, GSE8401 including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between metastatic melanoma and primary melanoma were screened using GEO2R. Assays of gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and protein-protein interaction (PPI) were performed to visualize these DEGs through Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools. Top 10 genes with high degree were defined as hub genes. Furthermore, paired post-metastatic melanoma cells and pre-metastatic melanoma cells were established by experimental mouse model of melanoma metastasis to verify the expression of these hub genes. Results 424 DEGs between the metastatic melanoma and primary melanoma were screened, including 60 upregulated genes enriched in ECM-receptor interaction and progesterone-mediated oocyte maturation and 364 downregulated genes enriched in amoebiasis, melanogenesis, and ECM-receptor interaction. CDH1, EGFR, KRT5, COL17A1, KRT14, IVL, DSP, DSG1, FLG and CDK1 were defined as the hub genes. . In addition, paired post-metastatic melanoma cells (A375M) and pre-metastatic melanoma cells (A375) were established and qRT-PCR analysis confirmed the expression of the hub genes during melanoma metastasis. Conclusion This bioinformatic study has provided a deeper understanding of the molecular mechanisms of melanoma metastasis. KRT5, IVL and COL17A1 have emerged as possible biomarkers and therapeutic targets in metastasis of melanoma.

scholarly journals Role of the Ubiquitin System in Chronic Pain

2021 ◽  
Vol 14 ◽  
Author(s):  
Jiurong Cheng ◽  
Yingdong Deng ◽  
Jun Zhou
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Public Health Issue ◽  
Deubiquitinating Enzyme ◽  
Ubiquitin System ◽  
Significant Public Health ◽  
Underlying Mechanisms ◽  
Insight Into

As a significant public health issue, chronic pain, mainly neuropathic pain (NP) and inflammatory pain, has a severe impact. The underlying mechanisms of chronic pain are enigmatic at present. The roles of ubiquitin have been demonstrated in various physiological and pathological conditions and underscore its potential as therapeutic targets. The dysfunction of the component of the ubiquitin system that occurs during chronic pain is rapidly being discovered. These results provide insight into potential molecular mechanisms of chronic pain. Chronic pain is regulated by ubiquitination, SUMOylation, ubiquitin ligase, and deubiquitinating enzyme (DUB), etc. Insight into the mechanism of the ubiquitin system regulating chronic pain might contribute to relevant therapeutic targets and the development of novel analgesics.

scholarly journals A functional landscape of chronic kidney disease entities from public transcriptomic data

2018 ◽  
Author(s):  
Ferenc Tajti ◽  
Christoph Kuppe ◽  
Asier Antoranz ◽  
Mahmoud M. Ibrahim ◽  
Hyojin Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gene Expression Data ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kidney Tissue ◽  
Therapeutic Targets ◽  
Expression Data ◽  
Disease Entities

AbstractTo develop efficient therapies and identify novel early biomarkers for chronic kidney disease an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in CKD origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for nine kidney disease entities that account for a majority of CKD worldwide. We included data from five distinct studies and compared glomerular gene expression profiles to that of non-tumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms and conditions, that we mitigated with a bespoke stringent procedure. This allowed us to perform a global transcriptome-based delineation of different kidney disease entities, obtaining a landscape of their similarities and differences based on the genes that acquire a consistent differential expression between each kidney disease entity and nephrectomy tissue. Furthermore, we derived functional insights by inferring activity of signaling pathways and transcription factors from the collected gene expression data, and identified potential drug candidates based on expression signature matching. We validated representative findings by immunostaining in human kidney biopsies indicating e.g. that the transcription factor FOXM1 is significantly and specifically expressed in parietal epithelial cells in RPGN whereas not expressed in control kidney tissue. These results provide a foundation to comprehend the specific molecular mechanisms underlying different kidney disease entities, that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate this, we provide our results as a free interactive web application: https://saezlab.shinyapps.io/ckd_landscape/.Translational StatementChronic kidney disease is a combination of entities with different etiologies. We integrate and analyse transcriptomics analysis of glomerular from different entities to dissect their different pathophysiology, what might help to identify novel entity-specific therapeutic targets.

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