A systematic update to Circulating Extracellular Vesicles proteome; transcriptome and small RNA-ome as Glioma Diagnostic, Prognostic and Treatment-Response Biomarkers

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

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MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

Thrombosis and Haemostasis ◽

10.1055/s-0039-1693702 ◽

2019 ◽

Vol 119 (10) ◽

pp. 1563-1572 ◽

Cited By ~ 2

Author(s):

Stefan Stojkovic ◽

Anne Yaël Nossent ◽

Paul Haller ◽

Bernhard Jäger ◽

Kris G. Vargas ◽

...

Keyword(s):

Coronary Artery Disease ◽

Acute Coronary Syndrome ◽

Coronary Artery ◽

Treatment Response ◽

Platelet Function ◽

Ribonucleic Acids ◽

Coronary Syndrome ◽

Artery Disease ◽

Response Biomarkers

AbstractMicroribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

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3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Scientific Reports ◽

10.1038/s41598-019-49671-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 24

Author(s):

Sirisha Thippabhotla ◽

Cuncong Zhong ◽

Mei He

Keyword(s):

Cervical Cancer ◽

Cell Culture ◽

Cancer Patient ◽

Extracellular Vesicles ◽

Small Rna ◽

Small Rnas ◽

3D Culture ◽

Cervical Cancer Patient ◽

Tumor Biomarker

Abstract For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the “gold standard”. 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D- culture derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D- culture derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D- culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D- culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

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Characterization of the small RNA content of Trypanosoma cruzi extracellular vesicles

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2014.02.004 ◽

2014 ◽

Vol 193 (2) ◽

pp. 71-74 ◽

Cited By ~ 41

Author(s):

Ethel Bayer-Santos ◽

Fábio Mitsuo Lima ◽

Jeronimo Conceição Ruiz ◽

Igor C. Almeida ◽

José Franco da Silveira

Keyword(s):

Trypanosoma Cruzi ◽

Extracellular Vesicles ◽

Small Rna ◽

Rna Content

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Relationships of Alzheimer’s disease and apolipoprotein E genotypes with small RNA and protein cargo of brain tissue extracellular vesicles

10.1101/2020.12.12.20247890 ◽

2020 ◽

Author(s):

Yiyao Huang ◽

Tom A. P. Driedonks ◽

Lesley Cheng ◽

Andrey Turchinovich ◽

Harinda Rajapaksha ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Extracellular Vesicles ◽

Small Rna ◽

Apoe Genotype ◽

Tau Proteins ◽

Small Rna Sequencing ◽

Health Crisis ◽

Metabolic Functions ◽

Apolipoprotein E Genotypes

ABSTRACTAlzheimer’s disease (AD) is a public health crisis that grows as populations age. Hallmarks of this neurodegenerative disease include aggregation of beta-amyloid peptides and hyperphosphorylated tau proteins in the brain. Variants of the APOE gene are the greatest known risk factors for sporadic AD. As emerging players in AD pathophysiology, extracellular vesicles (EVs) contain proteins, lipids, and RNAs and are involved in disposal of cellular toxins and intercellular communication. AD-related changes in the molecular composition of EVs may contribute to pathophysiology and lend insights into disease mechanisms. We recently adapted a method for separation of brain-derived EVs (bdEVs) from post-mortem tissues. Using this method, we isolated bdEVs from AD patients with different APOE genotypes (n=23) and controls (n=7). bdEVs were counted, sized, and subjected to parallel small RNA sequencing and proteomic analysis. Numerous bdEV-associated RNAs and proteins correlated with AD pathology and APOE genotype. Some of the identified entities have been implicated previously in important AD-related pathways, including amyloid processing, neurodegeneration, and metabolic functions. These findings provide further evidence that bdEVs and their molecular cargo modulate development and progression of AD.

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exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer

10.1101/2020.09.28.20190009 ◽

2020 ◽

Author(s):

Navneet Dogra ◽

Mehmet Eren Ahsen ◽

Edgar Gonzalez Kozlova ◽

Tzu-yi Chen ◽

kimaada allette ◽

...

Keyword(s):

Prostate Cancer ◽

Differential Expression ◽

Extracellular Vesicles ◽

Small Rna ◽

Tumor Tissue ◽

Biomarker Discovery ◽

De Novo ◽

Culture Media ◽

Tumor Resection ◽

Small Rna Sequencing

Circulating extracellular vesicles (EVs) present in the bodily fluids of patients with cancer may provide non-invasive access to the tumor tissue. Yet, the transcriptomic lineage of tumor-derived EVs before and after tumor-resection remains poorly understood. Here, we established 60 total small RNA-sequencing profiles from 17 aggressive prostate cancer (PCa) patients tumor and adjacent normal tissue, and EVs isolated from urine, serum, and cancer cell culture media. We interrogated the key satellite alteration in tumor-derived EVs and found that resection of tumor prostate tissue leads to differential expression of reactive oxygen species (ROS), P53 pathways, inflammatory/cytokines, oncogenes, and tumor suppressor genes in the EV nanosatellites. Furthermore, we provide a set of novel EV-specific RNA signature, which are present in cancer but are nonexistent in post-resection patients with undetectable cancer. Finally, using a de novo RNAseq assembly followed by characterization of the small RNA landscape, we found novel small RNA clusters (smRCs) in the EVs, which reside in the unannotated regions. Novel smRCs were orthogonally validated for their differential expression in the biomarker discovery cohort using RT-qPCR. We demonstrate that circulating tumor EVs provide a glimpse of the tumor tissue biology, resolving a major bottleneck in the current liquid biopsy efforts. Secretory vesicles appear to be playing a key role in non-canonical Wnt signaling and miRNA pathways, similar to the circulating tumor cells (CTCs), hence, we propose that such vesicles be called circulating tumor extracellular vesicles (CTEVs).

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