scholarly journals Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Jinwu Peng ◽  
Qiuju Liang ◽  
Zhijie Xu ◽  
Yuan Cai ◽  
Bi Peng ◽  
...  
Keyword(s):  
Immune Regulation ◽  
Response Prediction ◽  
Cell Types ◽  
Clinicopathological Characteristics ◽  
The Novel ◽  
Multiple Cancer ◽  
Exosomal Mirnas ◽  
Multiple Cell ◽  
Almost All ◽  
Therapeutic Responses

Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.

scholarly journals Mutational signature SBS8 predominantly arises due to late replication errors in cancer

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Vinod Kumar Singh ◽  
Arnav Rastogi ◽  
Xiaoju Hu ◽  
Yaqun Wang ◽  
Subhajyoti De
Keyword(s):  
Dna Repair ◽  
Cancer Progression ◽  
Replication Timing ◽  
Cell Types ◽  
Late Replication ◽  
Multiple Cancer ◽  
Mutational Signatures ◽  
Replication Errors ◽  
Mutational Signature ◽  
Multiple Cell

AbstractAlthough a majority of somatic mutations in cancer are passengers, their mutational signatures provide mechanistic insights into mutagenesis and DNA repair processes. Mutational signature SBS8 is common in most cancers, but its etiology is debated. Incorporating genomic, epigenomic, and cellular process features for multiple cell-types we develop genome-wide composite epigenomic context-maps relevant for mutagenesis and DNA repair. Analyzing somatic mutation data from multiple cancer types in their epigenomic contexts, we show that SBS8 preferentially occurs in gene-poor, lamina-proximal, late replicating heterochromatin domains. While SBS8 is uncommon among mutations in non-malignant tissues, in tumor genomes its proportions increase with replication timing and speed, and checkpoint defects further promote this signature - suggesting that SBS8 probably arises due to uncorrected late replication errors during cancer progression. Our observations offer a potential reconciliation among different perspectives in the debate about the etiology of SBS8 and its relationship with other mutational signatures.

scholarly journals c-Kit suppresses atherosclerosis in hyperlipidemic mice

2019 ◽  
Vol 317 (4) ◽  
pp. H867-H876 ◽  
Author(s):  
Lei Song ◽  
Zachary M. Zigmond ◽  
Laisel Martinez ◽  
Roberta M. Lassance-Soares ◽  
Alejandro E. Macias ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Cell Types ◽  
The Novel ◽  
Contractile Phenotype ◽  
Atp Binding Cassette Transporter ◽  
Lipid Efflux ◽  
Cardiovascular Morbidity And Mortality ◽  
Multiple Cell ◽  
Arterial Endothelial Cells

Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase family, which regulates differentiation, proliferation, and survival of multiple cell types. Recent studies have shown that c-Kit and its ligand stem cell factor (SCF) are present in arterial endothelial cells and smooth muscle cells (SMCs). The role of c-Kit in cardiovascular disease remains unclear. The aim of the current study is to determine the role of c-Kit in atherogenesis. For this purpose, atherosclerotic plaques were quantified in c-Kit-deficient mice (KitMut) after they were fed a high-fat diet (HFD) for 16 wk. KitMut mice demonstrated substantially greater atherosclerosis compared with control (KitWT) littermates ( P < 0.01). Transplantation of c-Kit-positive bone marrow cells into KitMut mice failed to rescue the atherogenic phenotype, an indication that increased atherosclerosis was associated with reduced arterial c-Kit. To investigate the mechanism, SMC organization and morphology were analyzed in the aorta by histopathology and electron microscopy. SMCs were more abundant, disorganized, and vacuolated in aortas of c-Kit mutant mice compared with controls ( P < 0.05). Markers of the “contractile” SMC phenotype (calponin, SM22α) were downregulated with pharmacological and genetic c-Kit inhibition ( P < 0.05). The absence of c-Kit increased lipid accumulation and significantly reduced the expression of the ATP-binding cassette transporter G1 (ABCG1) necessary for lipid efflux in SMCs. Reconstitution of c-Kit in cultured KitMut SMCs resulted in increased spindle-shaped morphology, reduced proliferation, and elevated levels of contractile markers, all indicators of their restored contractile phenotype ( P < 0.05). NEW & NOTEWORTHY This study describes the novel vasculoprotective role of c-Kit against atherosclerosis and its function in the preservation of the SMC contractile phenotype.

scholarly journals Exosomal MiRNAs in Pediatric Cancers

2019 ◽  
Vol 20 (18) ◽  
pp. 4600 ◽  
Author(s):  
Angela Galardi ◽  
Marta Colletti ◽  
Virginia Di Paolo ◽  
Patrizia Vitullo ◽  
Loretta Antonetti ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Aberrant Expression ◽  
Pediatric Cancers ◽  
Exosomal Mirnas ◽  
Rhabdoid Tumors ◽  
Almost All ◽  
Invasive Techniques ◽  
Different Cell Types

MicroRNAs (miRNAs) have generated great attention in oncology as they play a fundamental role in the regulation of gene expression and their aberrant expression is present in almost all types of tumors including pediatric ones. The discovery that miRNAs can be transported by exosomes, which are vesicles of 40–120 nm involved in cellular communication, that are produced by different cell types, and that are present in different biological fluids, has opened the possibility of using exosomal miRNAs as biomarkers. The possibility to diagnose and monitor the progression and response to drugs through molecules that can be easily isolated from biological fluids represents a particularly important aspect in the pediatric context where invasive techniques are often used. In recent years, the idea of liquid biopsy as well as studies on the possible role of exosomal miRNAs as biomarkers have developed greatly. In this review, we report an overview of all the evidences acquired in recent years on the identification of exosomal microRNAs with biomarker potential in pediatric cancers. We discuss the following herein: neuroblastoma, hepatoblastoma, sarcomas (osteosarcoma, Ewing’s sarcoma and rhabdoid tumors, and non-rhabdomyosarcoma soft tissue sarcoma), brain tumors, lymphomas, and leukemias.

scholarly journals The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinyan Wang ◽  
Lijuan Chen ◽  
Ping Qiang
Keyword(s):  
Rna Binding ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Cancer Prognosis ◽  
Messenger Rnas ◽  
Multiple Cancer ◽  
Multiple Cell ◽  
Mrna Binding ◽  
Post Transcriptional Regulation

AbstractThe human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application

2014 ◽  
Vol 395 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Takeshi Katsuda ◽  
Shingo Ikeda ◽  
Yusuke Yoshioka ◽  
Nobuyoshi Kosaka ◽  
Masaki Kawamata ◽  
...  
Keyword(s):  
Clinical Application ◽  
Cancer Progression ◽  
Immune Regulation ◽  
Tissue Repair ◽  
Cell Types ◽  
Clinical Applications ◽  
Research Field ◽  
Biological Processes ◽  
Exosomal Mirnas ◽  
Significant Attention

Abstract MicroRNAs (miRNAs) have attracted significant attention because of their important roles in a variety of physiological and pathological processes. Recent studies have shown that many cell types secrete miRNAs by packaging them into lipid-bilayered small vesicles called exosomes. Furthermore, exosomal miRNAs travel between cells, exert their RNAi effects in the recipient cells, and play important roles in various biological processes. In this article, we will summarize and describe the latest studies on exosomal miRNAs by focusing on their roles in cancer progression, immune regulation, and tissue repair. We will also provide a perspective on the clinical applications of this research field.

scholarly journals Exosomes: A Key Piece in Asthmatic Inflammation

2021 ◽  
Vol 22 (2) ◽  
pp. 963
Author(s):  
José A. Cañas ◽  
José M. Rodrigo-Muñoz ◽  
Marta Gil-Martínez ◽  
Beatriz Sastre ◽  
Victoria del Pozo
Keyword(s):  
Cell Types ◽  
Donor Cells ◽  
Wide Range ◽  
Spherical Structures ◽  
Multiple Cell ◽  
Extracellular Microenvironment ◽  
Almost All ◽  
Multiple Cells ◽  
Different Sources

Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.

Diligent Notes on Laziness: Oblomov, Lenin and the Capitalization of Laziness

2019 ◽  
Vol 29 (1) ◽  
pp. 243-258
Keyword(s):  
Psychiatric Hospital ◽  
The Novel ◽  
Work Analysis ◽  
Main Obstacle ◽  
Almost All ◽  
Russian Linguistic ◽  
The Way

The essay investigates the phenomenon of laziness by first analyzing the opposition between laziness and the good. Both utility and the good make reference to labor. This opposition between labor and laziness is pivotal in Oblomov, Ivan Goncharov’s famous novel written in 1859. It marks a radical transition from a feudal paradigm to a capitalistic one. The two main characters in the novel are Ilya Ilyich Oblomov, a Russian, and Andrey Ivanovich Stolz, a German, who together seem to personify the contradiction between laziness and labor. But the purpose of the essay is to deconstruct that opposition. In this connection, one can cite Kazimir Malevich, who maintained that laziness is the Mother of Perfection and is always unconsciously inherent in the conscious intent to work. Analysis of the Latin concepts of otium and negotium indicates that the laziness/labor opposition may be deconstructed as a dialectic between labor and its opposite. In other words, laziness does not stand in contradiction to labor but is instead its inseparable dialectical other. In the last part of the essay, the article considers the thinking of Anatoly Peregud, a poet who spent almost all his life in a psychiatric hospital. According to Peregud, Lenin derived his pseudonym from the Russian linguistic root “len” (laziness) in order to make laziness central to communism. For his part, Lenin saw Oblomov as an emblem of the main obstacle standing in the way of communism.

scholarly journals Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms

2021 ◽  
Vol 3 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Alexandra A. C. Newman ◽  
Vlad Serbulea ◽  
Richard A. Baylis ◽  
Laura S. Shankman ◽  
Xenia Bradley ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Cell Types ◽  
Fibrous Cap ◽  
Multiple Cell

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

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