Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?

Martellucci, Stefano; Orefice, Nicola Salvatore; Angelucci, Adriano; Luce, Amalia; Caraglia, Michele; Zappavigna, Silvia

doi:10.3390/ijms21186486

Cited by 42 publications

(32 citation statements)

References 171 publications

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“…Hence, another way to improve reliability of results in future preclinical studies could implicate the use of organoids, which can resemble histological and genetic characteristics of OC [ 56 ]. Lastly, the relevance of studying miRNAs in OC or other cancers is not limited only to an informative function, but extends also to their potential as future therapeutical targets, especially as modulators of chemoresistance [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

Krasniqi

Sacconi²,

Marinelli³

et al. 2021

Biomark Res

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Background In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

Krasniqi

Sacconi²,

Marinelli³

et al. 2021

Biomark Res

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“…EVs were loaded with siRNA by electroporation and for targeting, RVG peptides were attached to the surface via fusion with an exosomal marker protein and were used to deliver siRNA to mouse brains intravenously, indicating the capability of EV delivery systems to cross the blood brain barrier and, specifically, enter neurons, microglia and oligodendrocytes in the brain [ 19 ]. Mostly, small non-coding RNA species are used in EV-based delivery strategies [ 20 , 21 , 22 ]; however, linear DNA was also reported to associate with EVs [ 23 ].…”

Section: Introduction: Viral Vectors and Extracellular Vesiclesmentioning

confidence: 99%

On the Relationship of Viral Particles and Extracellular Vesicles: Implications for Viral Vector Technology

Metzner

Zaruba

2021

Viruses

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Gene therapy vectors derived from different viral species have become a fixture in biomedicine, both for direct therapeutic intervention and as tools to facilitate cell-based therapies, such as chimeric antigen receptor-based immunotherapies. On the contrary, extracellular vesicles have only recently gained a massive increase in interest and, concomitantly, knowledge in the field has drastically risen. Viral infections and extracellular vesicle biology overlap in many ways, both with pro- and antiviral outcomes. In this review, we take a closer look at these interactions for the most prominent groups of viral vectors (Adenoviral, Adeno-associated and Retro/Lentiviral vectors) and the possible implications of these overlaps for viral vector technology and its biomedical applications.

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“…Exosomes and other micro-vehicles have been found to shuttle DNA, RNA, and even protein to target cells 62 and influence cell phenotype. 63 Considering the complexity of pinpointing the specific pro-fibrotic component, the current study mainly focused on the general effect of serum. Further researches are necessary to figure out which factors in the serum play a role in this regulation.…”

Section: Discussionmentioning

confidence: 99%

The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation

Sun

Lin

Luo

et al. 2021

JIR

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Disorders with systematic inflammation were prognostic for secondary frozen shoulder (sFS) following rotator cuff repair (RCR); however, how systematic inflammation affects sFS remains unclear. The aim of this study was to observe the effect of pre-operative serum from patients with sFS and the serum from those without on shoulder capsule in mice, and on macrophages and fibroblasts in vitro. Methods: Serum samples of a consecutive cohort of patients for RCR were collected preoperatively. Three months after RCR, patients who developed sFS (Group S) were identified. Serum samples from gender-and age-matched controls without sFS (group NS) were also picked out. Firstly, the effect of serum on shoulder capsule fibrosis was observed histologically and biomechanically in a mouse model of RCR. Secondly, the roles of the serum on macrophage polarization and fibroblast activation were investigated, and the potentially involved signaling pathways were identified. Finally, inflammation and fibrosis-related cytokines in serum were quantified. Results: In our cohort, all patients had free pre-operative shoulder range of motion. Seven patients developed sFS at 3 months after surgery. Seven matched patients without sFS were selected as control. The inter-group difference of basic characteristics was not significant. Compared to the serum of group NS, the serum of group S significantly induced hypercellularity, capsular thickening, and range of motion deficiency in mice shoulders after RCR. Compared to the serum of group NS, samples of group S significantly promoted M2 polarization of THP-1 human macrophages and the activation of human capsule-derived fibroblasts. Meanwhile, Smad3 and p-Smad3 in macrophages and fibroblasts were significantly up-regulated. On the other hand, levels of inflammation and fibrosis-related cytokines were not significantly different between serum in group S and group NS. Conclusion: Although all patients in this cohort had free range of motion pre-operatively, the pre-operative serum from patients with sFS at 3 months after RCR could act as a trigger of shoulder capsule fibrosis post-operatively. This effect may be related to its promotion on macrophage polarization to M2 phenotype and fibroblast activation.

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Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy?

Cited by 42 publications

References 171 publications

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

On the Relationship of Viral Particles and Extracellular Vesicles: Implications for Viral Vector Technology

The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation

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