scholarly journals Targeting miR-9 in Glioma Stem Cell-Derived Extracellular Vesicles: A Novel Diagnostic and Therapeutic Biomarker

2021 ◽  
Author(s):  
Liangyuan Geng ◽  
Jinjin Xu ◽  
Yihao Zhu ◽  
Xinhua Hu ◽  
Yong Liu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Culture Medium ◽  
Expression Profiles ◽  
Wound Healing Assay ◽  
Malignant Phenotype ◽  
Gene Target ◽  
Effective Strategies ◽  
Mirna Expression Profiles ◽  
Proliferation Ability ◽  
And Migration

Abstract Background Glioblastoma, the lethal brain tumor with undesirable prognosis, still has no effective strategies in early diagnosis and treatment. Extracellular vesicles (EVs) isolated from cerebrospinal fluid (CSF) are a potential liquid biopsy source. This study was performed to assess the miRNA expression profiles in EVs from CSF and tissue of GBM patients to identify significantly upregulated miRNAs and investigate the underlying neoplastic mechanisms.Methods EVs were measured by TEM and NTA assays. Differentially regulated miRNAs were measured using RNA sequencing in GBM CSF EVs and in GBM tissues compared with controls. RT-qPCR was employed to analyze certain miRNA and gene expression. Luciferase report assay was used in investigate downstream gene target of miR-9. The proliferation ability was detected by EdU and CCK-8 experiment while cell migration was measured by transwell and wound healing assay.Results The expression level of miR-9 was significantly higher in GBM CSF EVs and tissues than controls (p = 0.038). The area under curve for CSF EV miR-9 was 0.080 (95% CI: 0.583–1.000, p = 0.033). The expression of miR-9 was significantly higher in GSCs and GSC-derived EVs compared with glioblastoma cells. GSC culture medium, which contained the GSC-derives EVs, could promote GBM growth and migration after administration to GBM cells. Moreover, inhibition of miR-9 in GSCs showed the reverse anti-tumor effects. MiR-9 could bind to the 3’UTR region of DACT3 and suppress its expression. The miR-9/DACT3 axis might attribute to GBM malignant phenotype.Conclusion MiR-9 in CSF EVs might act as a novel diagnostic biomarker for GBM and targeting miR-9 by GSC-derived EVs may be a specific and efficient strategy for GBM biotherapy.

scholarly journals Relevance of MicroRNAs as Potential Diagnostic and Prognostic Markers in Colorectal Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2944 ◽  
Author(s):  
Grzegorz Hibner ◽  
Małgorzata Kimsa-Furdzik ◽  
Tomasz Francuz
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Developed Countries ◽  
Prognostic Biomarkers ◽  
Screening Methods ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Mirna Expression Profiles ◽  
And Migration

Colorectal cancer (CRC) is currently the third and the second most common cancer in men and in women, respectively. Every year, more than one million new CRC cases and more than half a million deaths are reported worldwide. The majority of new cases occur in developed countries. Current screening methods have significant limitations. Therefore, a lot of scientific effort is put into the development of new diagnostic biomarkers of CRC. Currently used prognostic markers are also limited in assessing the effectiveness of CRC therapy. MicroRNAs (miRNAs) are a promising subject of research especially since single miRNA can recognize a variety of different mRNA transcripts. MiRNAs have important roles in epigenetic regulation of basic cellular processes, such as proliferation, apoptosis, differentiation, and migration, and may serve as potential oncogenes or tumor suppressors during cancer development. Indeed, in a large variety of human tumors, including CRC, significant distortions in miRNA expression profiles have been observed. Thus, the use of miRNAs as diagnostic and prognostic biomarkers in cancer, particularly in CRC, appears to be an inevitable consequence of the advancement in oncology and gastroenterology. Here, we review the literature to discuss the potential usefulness of selected miRNAs as diagnostic and prognostic biomarkers in CRC.

scholarly journals Extracellular Vesicles from Epicardial Fat Facilitate Atrial Fibrillation

Circulation ◽  
2021 ◽  
Author(s):  
Olga Shaihov-Teper ◽  
Eilon Ram ◽  
Nimer Ballan ◽  
Rafael Y. Brzezinski ◽  
Nili Naftali-Shani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Culture Medium ◽  
Heart Surgery ◽  
Biological Effects ◽  
Induced Pluripotent Stem Cell ◽  
Epicardial Fat ◽  
Human Mscs ◽  
And Migration

Background: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. Methods: We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. eFat samples were grown as organ cultures, and the culture medium was collected every two days. We then isolated and purified eFat-EVs from the culture medium, and analyzed the EV number, size, morphology, specific markers, encapsulated cytokines, proteome, and miRNAs. Next, we evaluated the biological effects of unpurified and purified EVs on atrial mesenchymal stromal cells (MSCs) and endothelial cells (ECs) in vitro. To establish a causal association between eFat-EVs and vulnerability to AF, we modeled AF in vitro using induced pluripotent stem cell-derived cardiomyocytes (iCMs). Results: Microscopic examination revealed excessive inflammation, fibrosis, and apoptosis in fresh and cultured eFat tissues. Cultured explants from patients with AF secreted more EVs and harbored greater amounts of proinflammatory and profibrotic cytokines, as well as profibrotic miRNA, than those without AF. The proteomic analysis confirmed the distinctive profile of purified eFat-EVs from patients with AF. In vitro, purified and unpurified eFat-EVs from patients with AF had a greater effect on proliferation and migration of human MSCs and ECs, compared to eFat-EVs from patients without AF. Finally, while eFat-EVs from patients with and without AF shortened the action potential duration of iCMs, only eFat-EVs from patients with AF induced sustained reentry (rotor) in iCMs. Conclusions: We show, for the first time, a distinctive proinflammatory, profibrotic, and proarrhythmic signature of eFat-EVs from patients with AF. Our findings uncover another pathway by which eFat promotes the development of atrial myopathy and fibrillation.

scholarly journals Clinicopathological-Associated Regulatory Network of Deregulated circRNAs in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2772
Author(s):  
Jian Han ◽  
Thomas Thurnherr ◽  
Alexander Y. F. Chung ◽  
Brian K. P. Goh ◽  
Pierce K. H. Chow ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Transformation ◽  
Expression Profiles ◽  
Cancer Pathways ◽  
Mirna Expression Profiles ◽  
Novel Strategy ◽  
And Migration ◽  
Identification And Characterization

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Here, we present a novel strategy to identify key circRNA signatures of clinically relevant co-expressed circRNA-mRNA networks in pertinent cancer-pathways that modulate prognosis of HCC patients, by integrating clinic-pathological features, circRNA and mRNA expression profiles. Through further integration with miRNA expression profiles, clinically relevant competing-endogenous-RNA (ceRNA) networks of circRNA-miRNA-mRNAs were constructed. At least five clinically relevant nodal-circRNAs, co-expressed with numerous genes, were identified from the circRNA-mRNA networks. These nodal circRNAs upregulated proliferation (except circRaly) and transformation in cells. The most upregulated nodal-circRNA, circGPC3, associated with higher-grade tumors and co-expressed with 33 genes, competes with 11 mRNAs for two shared miRNAs. circGPC3 was experimentally demonstrated to upregulate cell-cycle and migration/invasion in both transformed and non-transformed liver cell-lines. circGPC3 was further shown to act as a sponge of miR-378a-3p to regulate APSM (Abnormal spindle-like microcephaly associated) expression and modulate cell transformation. This study identifies 5 key nodal master circRNAs in a clinically relevant circRNA-centric network that are significantly associated with poorer prognosis of HCC patients and promotes tumorigenesis in cell-lines. The identification and characterization of these key circRNAs in clinically relevant circRNA-mRNA and ceRNA networks may facilitate the design of novel strategies targeting these important regulators for better HCC prognosis.

scholarly journals Identification of extracellular vesicles and characterization of miRNA expression profiles in human blastocoel fluid

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
R. Battaglia ◽  
S. Palini ◽  
M. E. Vento ◽  
A. La Ferlita ◽  
M. J. Lo Faro ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profiles

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

scholarly journals miRNA expression profiles in liver grafts of HCV and HIV/HCV infected recipients, six months after liver transplantation

2021 ◽  
Author(s):  
Michela Bulfoni ◽  
Riccardo Pravisani ◽  
Emiliano Dalla ◽  
Daniela Cesselli ◽  
Masaaki Hidaka ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profiles

scholarly journals Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro

2020 ◽  
Vol 22 (1) ◽  
pp. 38
Author(s):  
Martina Gatti ◽  
Francesca Beretti ◽  
Manuela Zavatti ◽  
Emma Bertucci ◽  
Soraia Ribeiro Luz ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Extracellular Vesicles ◽  
Culture Medium ◽  
Cell Potential ◽  
Osteoblast Cell Line ◽  
Local Bone ◽  
Current Therapies ◽  
Amniotic Fluid Stem Cell ◽  
Related Proteins

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion—these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.

scholarly journals MicroRNA expression classification for pediatric multiple sclerosis identification

2021 ◽  
Author(s):  
Gabriella Casalino ◽  
Giovanna Castellano ◽  
Arianna Consiglio ◽  
Nicoletta Nuzziello ◽  
Gennaro Vessio
Keyword(s):  
Machine Learning ◽  
Multiple Sclerosis ◽  
Expression Profiles ◽  
Healthy Children ◽  
Multifactorial Diseases ◽  
Hyperactivity Disorder ◽  
Pediatric Multiple Sclerosis ◽  
Mirna Expression Profiles ◽  
Selection Algorithms ◽  
Expression Classification

Abstract MicroRNAs (miRNAs) are a set of short non-coding RNAs that play significant regulatory roles in cells. The study of miRNA data produced by Next-Generation Sequencing techniques can be of valid help for the analysis of multifactorial diseases, such as Multiple Sclerosis (MS). Although extensive studies have been conducted on young adults affected by MS, very little work has been done to investigate the pathogenic mechanisms in pediatric patients, and none from a machine learning perspective. In this work, we report the experimental results of a classification study aimed at evaluating the effectiveness of machine learning methods in automatically distinguishing pediatric MS from healthy children, based on their miRNA expression profiles. Additionally, since Attention Deficit Hyperactivity Disorder (ADHD) shares some cognitive impairments with pediatric MS, we also included patients affected by ADHD in our study. Encouraging results were obtained with an artificial neural network model based on a set of features automatically selected by feature selection algorithms. The results obtained show that models developed on automatically selected features overcome models based on a set of features selected by human experts. Developing an automatic predictive model can support clinicians in early MS diagnosis and provide new insights that can help find novel molecular pathways involved in MS disease.

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