scholarly journals Micro RNAs in Regulation of Cellular Redox Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6022
Author(s):  
Sylwia Ciesielska ◽  
Izabella Slezak-Prochazka ◽  
Patryk Bil ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Target Genes ◽  
Redox Homeostasis ◽  
Messenger Rnas ◽  
Cellular Redox ◽  
Cell Responses ◽  
Regulatory Circuits ◽  
Micro Rnas ◽  
Cellular Behaviors ◽  
Homeostasis Regulation ◽  
Thioredoxin Reductases

In living cells Reactive Oxygen Species (ROS) participate in intra- and inter-cellular signaling and all cells contain specific systems that guard redox homeostasis. These systems contain both enzymes which may produce ROS such as NADPH-dependent and other oxidases or nitric oxide synthases, and ROS-neutralizing enzymes such as catalase, peroxiredoxins, thioredoxins, thioredoxin reductases, glutathione reductases, and many others. Most of the genes coding for these enzymes contain sequences targeted by micro RNAs (miRNAs), which are components of RNA-induced silencing complexes and play important roles in inhibiting translation of their targeted messenger RNAs (mRNAs). In this review we describe miRNAs that directly target and can influence enzymes responsible for scavenging of ROS and their possible role in cellular redox homeostasis. Regulation of antioxidant enzymes aims to adjust cells to survive in unstable oxidative environments; however, sometimes seemingly paradoxical phenomena appear where oxidative stress induces an increase in the levels of miRNAs which target genes which are supposed to neutralize ROS and therefore would be expected to decrease antioxidant levels. Here we show examples of such cellular behaviors and discuss the possible roles of miRNAs in redox regulatory circuits and further cell responses to stress.

scholarly journals Using Context-Sensitive Text Mining to Identify miRNAs in Different Stages of Atherosclerosis

2019 ◽  
Vol 119 (08) ◽  
pp. 1247-1264 ◽  
Author(s):  
Markus Joppich ◽  
Christian Weber ◽  
Ralf Zimmer
Keyword(s):  
Data Analysis ◽  
Text Mining ◽  
High Throughput ◽  
Target Genes ◽  
Mirna Gene ◽  
Cell Types ◽  
Gene Interactions ◽  
Messenger Rnas ◽  
New Findings ◽  
Micro Rnas

790 human and mouse micro-RNAs (miRNAs) are involved in diseases. More than 26,428 miRNA–gene interactions are annotated in humans and mice. Most of these interactions are posttranscriptional regulations: miRNAs bind to the messenger RNAs (mRNAs) of genes and induce their degradation, thereby reducing the gene expression of target genes. For atherosclerosis, 667 miRNA–gene interactions for 124 miRNAs and 343 genes have been identified and described in numerous publications. Some interactions were observed through high-throughput experiments, others were predicted using bioinformatic methods, and some were determined by targeted experiments. Several reviews collect knowledge on miRNA–gene interactions in (specific aspects of) atherosclerosis.Here, we use our bioinformatics resource (atheMir) to give an overview of miRNA–gene interactions in the context of atherosclerosis. The interactions are based on public databases and context-based text mining of 28 million PubMed abstracts. The miRNA–gene interactions are obtained from more than 10,000 publications, of which more than 1,000 are in a cardiovascular disease context (266 in atherosclerosis). We discuss interesting miRNA–gene interactions in atherosclerosis, grouped by specific processes in different cell types and six phases of atherosclerotic progression. All evidence is referenced and easily accessible: Relevant interactions are provided by atheMir as supplementary tables for further evaluation and, for example, for the subsequent data analysis of high-throughput measurements as well as for the generation and validation of hypotheses. The atheMir approach has several advantages: (1) the evidence is easily accessible, (2) regulatory interactions are uniformly available for subsequent high-throughput data analysis, and (3) the resource can incrementally be updated with new findings.

The Role of Selenium in Oxidative Stress and in Nonthyroidal Illness Syndrome (NTIS): An Overview

2020 ◽  
Vol 27 (3) ◽  
pp. 423-449 ◽  
Author(s):  
Andrea Silvestrini ◽  
Alvaro Mordente ◽  
Giuseppe Martino ◽  
Carmine Bruno ◽  
Edoardo Vergani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Nonthyroidal Illness ◽  
Cellular Redox ◽  
Selenium Metabolism ◽  
Glutathione Peroxidases ◽  
Iodothyronine Deiodinases ◽  
Correct Function ◽  
Thioredoxin Reductases

Selenium is a trace element, nutritionally classified as an essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is extensively described here. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases. This review summarizes the main advances on oxidative stress with a focus on selenium metabolism and transport. Moreover, thyroid-related disorders are discussed, considering that the thyroid gland contains the highest selenium amount per gram of tissue, also for future possible therapeutic implication.

scholarly journals Computational Model for Predicting the Relationship Between Micro-RNAs and Their Target Messenger RNAs in Breast and Colon Cancers

2018 ◽  
Vol 17 ◽  
pp. 117693511878514
Author(s):  
Shinuk Kim
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Computational Method ◽  
Numerical Code ◽  
Messenger Rnas ◽  
Unknown Parameters ◽  
Micro Rnas ◽  
The Relationship

Motivation: Uncovering the relationship between micro-RNAs (miRNAs) and their target messenger RNAs (mRNAs) can provide critical information regarding the mechanisms underlying certain types of cancers. In this context, we have proposed a computational method, referred to as prediction analysis by optimization method (PAOM), to predict miRNA-mRNA relations using data from normal and cancer tissues, and then applying the relevant algorithms to colon and breast cancers. Specifically, we used 26 miRNAs and 26 mRNAs with 676 (= 26 × 26) relationships to be recovered as unknown parameters. Results: Optimization methods were used to detect 61 relationships in breast cancer and 32 relationships in colon cancer. Using sequence filtering, we detected 18 relationships in breast cancer and 15 relationships in colon cancer. Among the 18 relationships, CD24 is the target gene of let-7a and miR-98, and E2F1 is the target gene of miR-20. In addition, the frequencies of the target genes of miR-223, miR-23a, and miR-20 were significant in breast cancer, and the frequencies of the target genes of miR-17, miR-124, and miR-30a were found to be significant in colon cancer. Availability: The numerical code is available from the authors on request.

scholarly journals Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma

Tumor Biology ◽  
2018 ◽  
Vol 40 (5) ◽  
pp. 101042831877367 ◽  
Author(s):  
Bangly Soliman ◽  
Ahmed Salem ◽  
Mohamed Ghazy ◽  
Nourhan Abu-Shahba ◽  
Mahmoud El Hefnawi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Signaling Pathway ◽  
Functional Annotation ◽  
Target Genes ◽  
Target Prediction ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Micro Rnas ◽  
The Individual

Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks–linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein–protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

Mitochondria-Targeted Ratiometric Fluorescent Imaging of Cysteine

The Analyst ◽  
2021 ◽  
Author(s):  
Ya-Nan Wei ◽  
Bo Lin ◽  
Yang Shu ◽  
Jian-Hua Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Fluorescent Imaging ◽  
Oxygen Species ◽  
Cellular Redox ◽  
Critical Part ◽  
Physiological Processes

As an indispensable biothiol, cysteine (Cys) plays a critical part in cellular redox homeostasis, pathological and physiological processes. One of the main sources of reactive oxygen species (ROS) in human...

scholarly journals Genome-wide transcriptome profiling uncovers differential miRNAs and lncRNAs in ovaries of Hu sheep at different developmental stages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samina Shabbir ◽  
Prerona Boruah ◽  
Lingli Xie ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Mohsin Nawaz ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Differentially Expressed ◽  
Ovary Development ◽  
Estrogen Metabolism ◽  
Genome Wide ◽  
Micro Rnas ◽  
Hu Sheep

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

scholarly journals Candidate Genes for the High-Altitude Adaptations of Two Mountain Pine Taxa

2021 ◽  
Vol 22 (7) ◽  
pp. 3477
Author(s):  
Julia Zaborowska ◽  
Bartosz Łabiszak ◽  
Annika Perry ◽  
Stephen Cavers ◽  
Witold Wachowiak
Keyword(s):  
Population Structure ◽  
Candidate Genes ◽  
Genetic Basis ◽  
Redox Homeostasis ◽  
Snp Markers ◽  
Regulation Of Transcription ◽  
Single Nucleotide ◽  
Homeostasis Regulation ◽  
Genomic Regions ◽  
Mountain Plants

Mountain plants, challenged by vegetation time contractions and dynamic changes in environmental conditions, developed adaptations that help them to balance their growth, reproduction, survival, and regeneration. However, knowledge regarding the genetic basis of species adaptation to higher altitudes remain scarce for most plant species. Here, we attempted to identify such corresponding genomic regions of high evolutionary importance in two closely related European pines, Pinus mugo and P. uncinata, contrasting them with a reference lowland relative—P. sylvestris. We genotyped 438 samples at thousands of single nucleotide polymorphism (SNP) markers, tested their genetic differentiation and population structure followed by outlier detection and gene ontology annotations. Markers clearly differentiated the species and uncovered patterns of population structure in two of them. In P. uncinata three Pyrenean sites were grouped together, while two outlying populations constituted a separate cluster. In P. sylvestris, Spanish population appeared distinct from the remaining four European sites. Between mountain pines and the reference species, 35 candidate genes for altitude-dependent selection were identified, including such encoding proteins responsible for photosynthesis, photorespiration and cell redox homeostasis, regulation of transcription, and mRNA processing. In comparison between two mountain pines, 75 outlier SNPs were found in proteins involved mainly in the gene expression and metabolism.

scholarly journals miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Target Genes ◽  
Expression Profiles ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

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