scholarly journals Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells

2015 ◽  
Vol 112 (49) ◽  
pp. 15154-15159 ◽  
Author(s):  
Antoine Tanne ◽  
Luciana R. Muniz ◽  
Anna Puzio-Kuter ◽  
Katerina I. Leonova ◽  
Andrei V. Gudkov ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Statistical Physics ◽  
Noncoding Rnas ◽  
Direct Interaction ◽  
Repetitive Elements ◽  
Satellite Repeat ◽  
Cpg Dinucleotides ◽  
Associated Function ◽  
First Time

Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated RNA. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncRNAs functions as immunostimulatory “self-agonists” and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncRNAs arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncRNAs expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncRNA expression in cancers and their relationship to the tumor microenvironment.

scholarly journals Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction

2021 ◽  
Vol 22 (21) ◽  
pp. 12051
Author(s):  
Marcin Pęziński ◽  
Kamila Maliszewska-Olejniczak ◽  
Patrycja Daszczuk ◽  
Paula Mazurek ◽  
Paweł Niewiadomski ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Cancer Cells ◽  
Acetylcholine Receptor ◽  
Actin Filaments ◽  
Neuromuscular Disorders ◽  
Scaffold Protein ◽  
Crucial Component ◽  
Important Regulator ◽  
First Time

Currently, the etiology of many neuromuscular disorders remains unknown. Many of them are characterized by aberrations in the maturation of the neuromuscular junction (NMJ) postsynaptic machinery. Unfortunately, the molecular factors involved in this process are still largely unknown, which poses a great challenge for identifying potential therapeutic targets. Here, we identified Tks5 as a novel interactor of αdystrobrevin-1, which is a crucial component of the NMJ postsynaptic machinery. Tks5 has been previously shown in cancer cells to be an important regulator of actin-rich structures known as invadosomes. However, a role of this scaffold protein at a synapse has never been studied. We show that Tks5 is crucial for remodeling of the NMJ postsynaptic machinery by regulating the organization of structures similar to the invadosomes, known as synaptic podosomes. Additionally, it is involved in the maintenance of the integrity of acetylcholine receptor (AChR) clusters and regulation of their turnover. Lastly, our data indicate that these Tks5 functions may be mediated by its involvement in recruitment of actin filaments to the postsynaptic machinery. Collectively, we show for the first time that the Tks5 protein is involved in regulation of the postsynaptic machinery.

scholarly journals LitR directly upregulates autoinducer synthesis and luminescence in Aliivibrio logei

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12030
Author(s):  
Sergey Bazhenov ◽  
Olga Melkina ◽  
Vadim Fomin ◽  
Ekaterina Scheglova ◽  
Pavel Krasnik ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Main Role ◽  
Photorhabdus Luminescens ◽  
Psychrophilic Bacteria ◽  
System Effect ◽  
Aliivibrio Salmonicida ◽  
Aliivibrio Fischeri ◽  
First Time ◽  
Aliivibrio Logei

LitR is a master-regulator of transcription in the ainS/R and luxS/PQ quorum sensing (QS) systems of bacteria from Vibrio and Aliivibrio genera. Here, we for the first time directly investigated the influence of LitR on gene expression in the luxI/R QS system of psychrophilic bacteria Aliivibrio logei. Investigated promoters were fused with Photorhabdus luminescens luxCDABE reporter genes cassette in a heterological system of Escherichia coli cells, litR A. logei was introduced into the cells under control of Plac promoter. LitR has been shown to upregulate genes of autoinducer synthase (luxI), luciferase and reductase (luxCDABE), and this effect doesn’t depend on presence of luxR gene. To a much lesser degree, LitR induces luxR1, but not the luxR2 — the main luxI/R regulator. Enhanced litR expression leads to an increase in a LuxI-autoinducer synthesis and a subsequent LuxR-mediated activation of the luxI/R QS system. Effect of LitR on luxI transcription depends on lux-box sequence in luxI promoter even in absence of luxR (lux-box is binding site of LuxR). The last finding indicates a direct interaction of LitR with the promoter in the lux-box region. Investigation of the effect of LitR A. logei on luxI/R QS systems of mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio salmonicida showed direct luxR-independent upregulation of luxI and luxCDABE genes. To a lesser degree, it induces luxR A. fischeri and luxR1 A. salmonicida. Therefore, we assume that the main role of LitR in cross-interaction of these three QS systems is stimulating the expression of luxI.

scholarly journals Inhibition of  a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Author(s):  
Wanessa Altei ◽  
Bianca Pachane ◽  
Patty K. Santos ◽  
Ligia Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cd63 Expression ◽  
Cell Cell

Abstract Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for avb3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry avb3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of avb3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.Conclusion: In summary, our findings demonstrate for the first time a key role of avb3 integrin in cell-cell communication through SEVs.

scholarly journals Inhibition of  a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Author(s):  
Wanessa Altei ◽  
Bianca Pachane ◽  
Patty K. Santos ◽  
Ligia Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Αvβ3 Integrin ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cell Cell

Abstract Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells. Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments. Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content. Conclusion: In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs.

scholarly journals Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wanessa F. Altei ◽  
Bianca C. Pachane ◽  
Patty K. dos Santos ◽  
Lígia N. M. Ribeiro ◽  
Bong Hwan Sung ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Αvβ3 Integrin ◽  
Organ Specific ◽  
Breast Cells ◽  
Mediate Cell ◽  
First Time ◽  
Cell Cell

Abstract Background Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells. Methods To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments. Results We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content. Conclusion In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs. Graphical abstract

scholarly journals The function of LncRNA-H19 in cardiac hypertrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenhua Su ◽  
Qian Huo ◽  
Hao Wu ◽  
Lulin Wang ◽  
Xiaoxue Ding ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Adaptive Response ◽  
Molecular Mechanisms ◽  
Myocardial Hypertrophy ◽  
Noncoding Rnas ◽  
Biological Functions ◽  
Pathological Mechanism ◽  
First Time ◽  
Insight Into

AbstractCardiac hypertrophy, characterized by the enlargement of cardiomyocytes, is initially an adaptive response to physiological and pathological stimuli. Decompensated cardiac hypertrophy is related to fibrosis, inflammatory cytokine, maladaptive remodeling, and heart failure. Although pathological myocardial hypertrophy is the main cause of hypertrophy-related morbidity and mortality, our understanding of its mechanism is still poor. Long noncoding RNAs (lncRNAs) are noncoding RNAs that regulate various physiological and pathological processes through multiple molecular mechanisms. Recently, accumulating evidence has indicated that lncRNA-H19 is a potent regulator of the progression of cardiac hypertrophy. For the first time, this review summarizes the current studies about the role of lncRNA-H19 in cardiac hypertrophy, including its pathophysiological processes and underlying pathological mechanism, including calcium regulation, fibrosis, apoptosis, angiogenesis, inflammation, and methylation. The context within which lncRNA-H19 might be developed as a target for cardiac hypertrophy treatment is then discussed to gain better insight into the possible biological functions of lncRNA-H19 in cardiac hypertrophy.

scholarly journals Differential Expression of Long Noncoding RNAs Reveals a Potential Biomarker for Intractable Pemphigus

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Peng Qu ◽  
Zixuan Huang ◽  
Haiqin Zhu ◽  
Jie Zheng ◽  
Meng Pan
Keyword(s):  
Expression Profile ◽  
Operating Characteristic ◽  
Mononuclear Cells ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarker ◽  
First Time

Background. Long noncoding RNAs (lncRNAs) are involved in autoimmune diseases. However, the role of lncRNAs in pemphigus remains elusive. Objective. The study is aimed at investigating the expression profile in pemphigus patients to identify a circulating lncRNA as a novel biomarker for pemphigus. Method. A global lncRNA expression profile in peripheral blood mononuclear cells (PBMCs) was measured by lncRNA microarray. Differentially expressed lncRNAs were validated by quantitative reverse transcriptase-PCR (qRT-PCR). The functional and biological processes of the differentially expressed lncRNAs were analyzed by bioinformatics. Results. lncRNA ENST00000585297 in the PBMCs of pemphigus patients was highly expressed compared with those of HCs and BP patients. The area under the receiver operating characteristic (ROC) curve was 0.846 ( 95 % confidence   interval   CI = 0.7526 to 0.9397). Intriguingly, we found that the expression of ENST00000585297 was upregulated in pemphigus patients whose symptoms could not be managed within four weeks compared to other patients whose symptoms could be managed in four weeks or less ( P < 0.05 ). In addition, ENST00000585297 expression in pemphigus patients was positively correlated with the dosage of prednisone needed to manage the disorder ( r = 0.4905 , P = 0.0094 ). A competing endogenous RNA (ceRNA) regulatory network was constructed based on the ceRNA theory. Further verification demonstrated that silencing of ENST00000585297 increased the expression of miR-584-3p. Conclusions. Our study revealed for the first time the expression profile of lncRNAs in pemphigus patients. In addition, our study identified ENST00000585297 as a biomarker and indicator for the intractable course of pemphigus.

scholarly journals Noncoding RNAs in the Interplay between Tumor Cells and Cancer-Associated Fibroblasts: Signals to Catch and Targets to Hit

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 709
Author(s):  
Martina Tassinari ◽  
Paolo Gandellini
Keyword(s):  
Cancer Cells ◽  
Clinical Utility ◽  
Current Knowledge ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Tumor Stroma ◽  
Cancer Associated Fibroblasts ◽  
Cell Type ◽  
Physical Conditions

Cancer development and progression are not solely cell-autonomous and genetically driven processes. Dynamic interaction of cancer cells with the surrounding microenvironment, intended as the chemical/physical conditions as well as the mixture of non-neoplastic cells of the tumor niche, drive epigenetic changes that are pivotal for the acquisition of malignant traits. Cancer-associated fibroblasts (CAF), namely fibroblasts that, corrupted by cancer cells, acquire a myofibroblast-like reactive phenotype, are able to sustain tumor features by the secretion of soluble paracrine signals and the delivery extracellular vesicles. In such diabolic liaison, a major role has been ascribed to noncoding RNAs. Defined as RNAs that are functional though not being translated into proteins, noncoding RNAs predominantly act as regulators of gene expression at both the transcriptional and post-transcriptional levels. In this review, we summarize the current knowledge of microRNAs and long noncoding RNAs that act intracellularly in either CAFs or cancer cells to sustain tumor-stroma interplay. We also report on the major role of extracellular noncoding RNAs that are bidirectionally transferred between either cell type. Upon presenting a comprehensive view of the existing literature, we provide our critical opinion regarding the possible clinical utility of tumor-stroma related noncoding RNAs as therapeutic target/tools or prognostic/predictive biomarkers.

scholarly journals The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 627
Author(s):  
Han Yeoung Lee ◽  
Seung Wan Son ◽  
Sokviseth Moeng ◽  
Soo Young Choi ◽  
Jong Kook Park
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Noncoding Rnas ◽  
Health Concern ◽  
Anoikis Resistance ◽  
Patients With Cancer ◽  
Cancer Aggressiveness

Cancer is a global health concern, and the prognosis of patients with cancer is associated with metastasis. Multistep processes are involved in cancer metastasis. Accumulating evidence has shown that cancer cells acquire the capacity of anoikis resistance and anchorage-independent cell growth, which are critical prerequisite features of metastatic cancer cells. Multiple cellular factors and events, such as apoptosis, survival factors, cell cycle, EMT, stemness, autophagy, and integrins influence the anoikis resistance and anchorage-independent cell growth in cancer. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are dysregulated in cancer. They regulate cellular signaling pathways and events, eventually contributing to cancer aggressiveness. This review presents the role of miRNAs and lncRNAs in modulating anoikis resistance and anchorage-independent cell growth. We also discuss the feasibility of ncRNA-based therapy and the natural features of ncRNAs that need to be contemplated for more beneficial therapeutic strategies against cancer.

scholarly journals Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Praveen Sharma ◽  
Vibhuti Sharma ◽  
Tarunveer Singh Ahluwalia ◽  
Nilambra Dogra ◽  
Santosh Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mitochondrial Genome ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Metabolic Reprogramming ◽  
Mitochondrial Transcription ◽  
A Cell ◽  
First Time

Abstract Background and objectives MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.

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