Molecular pathways of Interferon–Stimulated Gene 15: Implications in cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Angeles C. Tecalco–Cruz
Keyword(s):  
Posttranslational Modification ◽  
Human Interferon ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Small Protein ◽  
Target Proteins ◽  
Central Elements ◽  
Cancer Types ◽  
Interferon Stimulated Gene 15

Abstract:: Human interferon–stimulated gene 15 (ISG15) is a 15–kDa ubiquitin–like protein that can be detected as either free ISG15 or covalently associated with its target proteins through a process termed ISGylation. Interestingly, extracellular free ISG15 has been proposed as a cytokine–like protein, whereas ISGylation is a posttranslational modification. ISG15 is a small protein with implications in some biological processes and pathologies that include cancer. This review highlights the findings of both free ISG15 and protein ISGylation involved in several molecular pathways, emerging as central elements in some cancer types.

scholarly journals The Role of Deubiquitinating Enzymes in the Various Forms of Autophagy

2020 ◽  
Vol 21 (12) ◽  
pp. 4196 ◽  
Author(s):  
Tamás Csizmadia ◽  
Péter Lőw
Keyword(s):  
Posttranslational Modification ◽  
Essential Role ◽  
Biological Processes ◽  
Deubiquitinating Enzymes ◽  
Cellular Homeostasis ◽  
Target Proteins

Deubiquitinating enzymes (DUBs) have an essential role in several cell biological processes via removing the various ubiquitin patterns as posttranslational modification forms from the target proteins. These enzymes also contribute to the normal cytoplasmic ubiquitin pool during the recycling of this molecule. Autophagy, a summary name of the lysosome dependent self-degradative processes, is necessary for maintaining normal cellular homeostatic equilibrium. Numerous forms of autophagy are known depending on how the cellular self-material is delivered into the lysosomal lumen. In this review we focus on the colorful role of DUBs in autophagic processes and discuss the mechanistic contribution of these molecules to normal cellular homeostasis via the possible regulation forms of autophagic mechanisms.

scholarly journals POS0458 IDENTIFICATION OF HUB GENES AND MOLECULAR PATHWAYS IN PATIENTS WITH RHEUMATOID ARTHRITIS BY BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 460.1-460
Author(s):  
L. Cheng ◽  
S. X. Zhang ◽  
S. Song ◽  
C. Zheng ◽  
X. Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Bioinformatics Analysis ◽  
Metabolic Process ◽  
Shanxi Province ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Hub Genes ◽  
Tissue Samples

Background:Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis based systemic disease of unknown etiology1. The genes and pathways in the inflamed synovium of RA patients are poorly understood.Objectives:This study aims to identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA using bioinformatics analysis and explore its pathogenesis2.Methods:RA expression profile microarray data GSE89408 were acquired from the public gene chip database (GEO), including 152 synovial tissue samples from RA and 28 healthy synovial tissue samples. The DEGs of RA synovial tissues were screened by adopting the R software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) networks were assembled with Cytoscape software.Results:A total of 654 DEGs (268 up-regulated genes and 386 down-regulated genes) were obtained by the differential analysis. The GO enrichment results showed that the up-regulated genes were significantly enriched in the biological processes of myeloid leukocyte activation, cellular response to interferon-gamma and immune response-regulating signaling pathway, and the down-regulated genes were significantly enriched in the biological processes of extracellular matrix, retinoid metabolic process and regulation of lipid metabolic process. The KEGG annotation showed the up-regulated genes mainly participated in the staphylococcus aureus infection, chemokine signaling pathway, lysosome signaling pathway and the down-regulated genes mainly participated in the PPAR signaling pathway, AMPK signaling pathway, ECM-receptor interaction and so on. The 9 hub genes (PTPRC, TLR2, tyrobp, CTSS, CCL2, CCR5, B2M, fcgr1a and PPBP) were obtained based on the String database model by using the Cytoscape software and cytoHubba plugin3.Conclusion:The findings identified the molecular mechanisms and the key hub genes of pathogenesis and progression of RA.References:[1]Xiong Y, Mi BB, Liu MF, et al. Bioinformatics Analysis and Identification of Genes and Molecular Pathways Involved in Synovial Inflammation in Rheumatoid Arthritis. Med Sci Monit 2019;25:2246-56. doi: 10.12659/MSM.915451 [published Online First: 2019/03/28][2]Mun S, Lee J, Park A, et al. Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry. Int J Mol Sci 2019;20(18) doi: 10.3390/ijms20184368 [published Online First: 2019/09/08][3]Zhu N, Hou J, Wu Y, et al. Identification of key genes in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis. Medicine (Baltimore) 2018;97(22):e10997. doi: 10.1097/MD.0000000000010997 [published Online First: 2018/06/01]Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis

2020 ◽  
Vol 6 (4) ◽  
pp. 42 ◽  
Author(s):  
Julia Teppan ◽  
Dominik A. Barth ◽  
Felix Prinz ◽  
Katharina Jonas ◽  
Martin Pichler ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Biological Processes ◽  
Protein Coding ◽  
Diagnostic Biomarkers ◽  
Oncogenic Pathways ◽  
Therapeutic Molecules ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Effective Use ◽  
To Receive

Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis. Angiogenesis, the formation of new blood vessels, is crucial for a tumor to receive sufficient amounts of nutrients and oxygen and therefore, to grow and exceed in its size over the diameter of 2 mm. In this review, the regulatory mechanisms of lncRNAs are described, which influence tumor angiogenesis by directly or indirectly regulating oncogenic pathways, interacting with other transcripts such as microRNAs (miRNAs) or modulating the tumor microenvironment. Further, angiogenic lncRNAs occurring in several cancer types such as liver, gastrointestinal cancer, or brain tumors are summarized. Growing evidence on the influence of lncRNAs on tumor angiogenesis verified these transcripts as potential predictive or diagnostic biomarkers or therapeutic targets of anti-angiogenesis treatment. However, there are many unsolved questions left which are pointed out in this review, hence driving comprehensive research in this area is necessary to enable an effective use of lncRNAs as either therapeutic molecules or diagnostic targets in cancer.

scholarly journals Retinoic Acids in the Treatment of Most Lethal Solid Cancers

2020 ◽  
Vol 9 (2) ◽  
pp. 360 ◽  
Author(s):  
Lara Costantini ◽  
Romina Molinari ◽  
Barbara Farinon ◽  
Nicolò Merendino
Keyword(s):  
Retinoic Acid ◽  
World Health ◽  
Solid Cancer ◽  
Molecular Pathways ◽  
Acid Therapy ◽  
Retinoic Acids ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cancer Types ◽  
Health Organization

Although the use of oral administration of pharmacological all-trans retinoic acid (ATRA) concentration in acute promyelocytic leukaemia (APL) patients was approved for over 20 years and used as standard therapy still to date, the same use in solid cancers is still controversial. In the present review the literature about the top five lethal solid cancers (lung, stomach, liver, breast, and colon cancer), as defined by The Global Cancer Observatory of World Health Organization, and retinoic acids (ATRA, 9-cis retinoic acid, and 13-cis retinoic acid, RA) was compared. The action of retinoic acids in inhibiting the cell proliferation was found in several cell pathways and compartments: from membrane and cytoplasmic signaling, to metabolic enzymes, to gene expression. However, in parallel in the most aggressive phenotypes several escape routes have evolved conferring retinoic acids-resistance. The comparison between different solid cancer types pointed out that for some cancer types several information are still lacking. Moreover, even though some pathways and escape routes are the same between the cancer types, sometimes they can differently respond to retinoic acid therapy, so that generalization cannot be made. Further studies on molecular pathways are needed to perform combinatorial trials that allow overcoming retinoic acids resistance.

scholarly journals Methylation of Histone 4's Lysine 20: A critical analysis of the state of the field

2020 ◽  
Author(s):  
Adriana Z. Corvalan ◽  
Hilary A. Coller
Keyword(s):  
Posttranslational Modification ◽  
Current Knowledge ◽  
Dynamic Structure ◽  
Future Research ◽  
Biological Processes ◽  
Histone H4 ◽  
Histone Tails ◽  
Nonhistone Proteins ◽  
Multiple Processes ◽  
Cycle Regulation

Chromatin is a highly dynamic structure whose plasticity is achieved through multiple processes including the posttranslational modification of histone tails. Histone modifications function through the recruitment of nonhistone proteins to chromatin and thus have the potential to influence many fundamental biological processes. Here, we focus on the function and regulation of lysine 20 of histone H4 (H4K20) methylation in multiple biological processes including DNA repair, cell cycle regulation and DNA replication. The purpose of this review is to highlight recent studies that elucidate the functions associated with each of the methylation states of H4K20, their modifying enzymes, and their protein readers. Based on our current knowledge of H4K20 methylation, we critically analyze the data supporting these functions and outline questions for future research.

scholarly journals Mutation Enrichment and Transcriptomic Activation Signatures of 419 Molecular Pathways in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 271 ◽  
Author(s):  
Marianna A. Zolotovskaia ◽  
Victor S. Tkachev ◽  
Alexander P. Seryakov ◽  
Denis V. Kuzmin ◽  
Dmitry E. Kamashev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Gene Networks ◽  
The Other ◽  
Molecular Pathways ◽  
Dna Mutations ◽  
Whole Exome ◽  
Pathway Activation ◽  
Cancer Types ◽  
First Time

Carcinogenesis is linked with massive changes in regulation of gene networks. We used high throughput mutation and gene expression data to interrogate involvement of 278 signaling, 72 metabolic, 48 DNA repair and 47 cytoskeleton molecular pathways in cancer. Totally, we analyzed 4910 primary tumor samples with individual cancer RNA sequencing and whole exome sequencing profiles including ~1.3 million DNA mutations and representing thirteen cancer types. Gene expression in cancers was compared with the corresponding 655 normal tissue profiles. For the first time, we calculated mutation enrichment values and activation levels for these pathways. We found that pathway activation profiles were largely congruent among the different cancer types. However, we observed no correlation between mutation enrichment and expression changes both at the gene and at the pathway levels. Overall, positive median cancer-specific activation levels were seen in the DNA repair, versus similar slightly negative values in the other types of pathways. The DNA repair pathways also demonstrated the highest values of mutation enrichment. However, the signaling and cytoskeleton pathways had the biggest proportions of representatives among the outstandingly frequently mutated genes thus suggesting their initiator roles in carcinogenesis and the auxiliary/supporting roles for the other groups of molecular pathways.

scholarly journals Integrated Analysis of Gene Network in Childhood Leukemia from Microarray and Pathway Databases

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Amphun Chaiboonchoe ◽  
Sandhya Samarasinghe ◽  
Don Kulasiri ◽  
Kourosh Salehi-Ashtiani
Keyword(s):  
Gene Network ◽  
Childhood Leukemia ◽  
Therapeutic Agents ◽  
Interaction Networks ◽  
Integrated Analysis ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Biological Insight ◽  
Insight Into ◽  
Pathway Databases

Glucocorticoids (GCs) have been used as therapeutic agents for children with acute lymphoblastic leukaemia (ALL) for over 50 years. However, much remains to be understood about the molecular mechanism of GCs actions in ALL subtypes. In this study, we delineate differential responses of ALL subtypes, B- and T-ALL, to GCs treatment at systems level by identifying the differences among biological processes, molecular pathways, and interaction networks that emerge from the action of GCs through the use of a selected number of available bioinformatics methods and tools. We provide biological insight into GC-regulated genes, their related functions, and their networks specific to the ALL subtypes. We show that differentially expressed GC-regulated genes participate in distinct underlying biological processes affected by GCs in B-ALL and T-ALL with little to no overlap. These findings provide the opportunity towards identifying new therapeutic targets.

scholarly journals Dicer-to-Argonaute switch controls biogenesis of oncogenic miRNA

2021 ◽  
Author(s):  
Francesca M Buffa ◽  
Laura Winchester ◽  
Linda van Bijsterveldt ◽  
Andrew Dhawan
Keyword(s):  
Cancer Progression ◽  
Experimental Validation ◽  
Transcriptional Regulators ◽  
Clinical Samples ◽  
Mirna Biogenesis ◽  
Integrated Analysis ◽  
Biological Processes ◽  
Independent Manner ◽  
Driver Pathway ◽  
Cancer Types

miRNAs are post-transcriptional regulators of gene expression, controlling biological processes from development to pathogenesis. We asked whether the reshaped functional miRNA landscape in cancers is driven by altered transcription of its precursors, or altered biogenesis and maturation of miRNAs. Integrated analysis of genomic and transcriptomic data in 9,111 samples across 10 cancer types and healthy tissues revealed a recurrent genomic switch from DICER-dependent to non-canonical Argonaute-mediated, DICER-independent, miRNA biogenesis. Experimental validation in AGO2-amplified clinical samples and cancer cell lines confirmed that canonical miRNAs can undergo maturation in a DICER-independent manner, and that elevated Argonaute levels promote selective maturation of the oncogenic miR-106b/25 cluster as shown by the altered ratio of mature miRNA to immature pri-miRNA levels. The preferential maturation of these oncogenic miRNAs, whose processing bypasses DICER1, promotes cancer progression and predicts poor prognosis. This highlights the evolution of non-canonical AGO2-dependent oncomiR processing as a novel driver pathway in cancer.

scholarly journals Long non-coding RNAs as pan-cancer master gene regulators of associated protein-coding genes: a systems biology approach

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6388 ◽  
Author(s):  
Asanigari Saleembhasha ◽  
Seema Mishra
Keyword(s):  
Gene Expression ◽  
Gene Expression Pattern ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Lncrna Gene ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Rna Interaction ◽  
Pan Cancer

Despite years of research, we are still unraveling crucial stages of gene expression regulation in cancer. On the basis of major biological hallmarks, we hypothesized that there must be a uniform gene expression pattern and regulation across cancer types. Among non-coding genes, long non-coding RNAs (lncRNAs) are emerging as key gene regulators playing powerful roles in cancer. Using TCGA RNAseq data, we analyzed coding (mRNA) and non-coding (lncRNA) gene expression across 15 and 9 common cancer types, respectively. 70 significantly differentially expressed genes common to all 15 cancer types were enlisted. Correlating with protein expression levels from Human Protein Atlas, we observed 34 positively correlated gene sets which are enriched in gene expression, transcription from RNA Pol-II, regulation of transcription and mitotic cell cycle biological processes. Further, 24 lncRNAs were among common significantly differentially expressed non-coding genes. Using guilt-by-association method, we predicted lncRNAs to be involved in same biological processes. Combining RNA-RNA interaction prediction and transcription regulatory networks, we identified E2F1, FOXM1 and PVT1 regulatory path as recurring pan-cancer regulatory entity. PVT1 is predicted to interact with SYNE1 at 3′-UTR; DNAJC9, RNPS1 at 5′-UTR and ATXN2L, ALAD, FOXM1 and IRAK1 at CDS sites. The key findings are that through E2F1, FOXM1 and PVT1 regulatory axis and possible interactions with different coding genes, PVT1 may be playing a prominent role in pan-cancer development and progression.

scholarly journals Quantitative proteomics reveals extensive lysine ubiquitination in the Arabidopsis root proteome and uncovers novel transcription factor stability states

2021 ◽  
Author(s):  
Gaoyuan Song ◽  
Damilola Olatunji ◽  
Christian Montes ◽  
Natalie M Clark ◽  
Yunting Pu ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Site Directed Mutagenesis ◽  
Biological Processes ◽  
Protein Activity ◽  
Helix Loop Helix ◽  
Primary Roots ◽  
Lysine Residues ◽  
Ubiquitin Proteasome ◽  
The Stability

Protein activity, abundance, and stability can be regulated by posttranslational modification including ubiquitination. Ubiquitination is conserved among eukaryotes and plays a central role in modulating cellular function and yet we lack comprehensive catalogs of proteins that are modified by ubiquitin in plants. In this study, we describe an antibody-based approach to enrich peptides containing the di-glycine (diGly) remnant of ubiquitin and coupled that with isobaric labeling to enable quantification, from up to 16-multiplexed samples, for plant tissues. Collectively, we identified 7,130 diGly-modified lysine residues sites arising from 3,178 proteins in Arabidopsis primary roots. These data include ubiquitin proteasome dependent ubiquitination events as well as ubiquitination events associated with auxin treatment. Gene Ontology analysis indicated that ubiquitinated proteins are associated with numerous biological processes including hormone signaling, plant defense, protein homeostasis, and root morphogenesis. We determined the ubiquitinated lysine residues that directly regulate the stability of the transcription factors CRYPTOCHROME-INTERACTING BASIC-HELIX-LOOP-HELIX 1 (CIB1), CIB1 LIKE PROTEIN 2 (CIL2), and SENSITIVE TO PROTON RHIZOTOXICITY (STOP1) using site directed mutagenesis and in vivo degradation assays. These comprehensive site-level ubiquitinome profiles provide a wealth of data for future studies related to modulation of biological processes mediated by this posttranslational modification in plants.

Sign in / Sign up

Export Citation Format

Share Document