Exosomal MiRNAs in Pediatric Cancers

Galardi, Angela; Colletti, Marta; Paolo, Virginia Di; Vitullo, Patrizia; Antonetti, Loretta; Russo, Ida; Giannatale, Angela Di

doi:10.3390/ijms20184600

Cited by 45 publications

(39 citation statements)

References 146 publications

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“…The above results suggested that circ_0000527 was involved in promoting the progression of RB and demonstrated that it had an important role in RB. MiRNAs are also reported to be engaged in the regulation of the tumorigenesis and progression of a variety of human tumors [25,26]. MiR-646 is regarded as a tumor suppressor in many human cancers.…”

Section: Discussionmentioning

confidence: 99%

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Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Zhang¹,

Wu²,

Li³

et al. 2020

Cancer Cell Int

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Background: Researches validate that circular RNAs (circRNAs) are dysregulated in a variety of malignancies and play an important role in regulating the malignant phenotype of tumor cells. Nevertheless, the role of circ_0000527 in retinoblastoma (RB) and its regulatory mechanisms remain largely unknown. Methods: Real-time PCR (RT-PCR) was used to detect circ_0000527 and miR-646 expression in RB tissues and cells. The LRP6 expression in RB cells was detected by Western blot. The relationship between circ_0000527 expression and the clinicopathological parameters of RB patients was analyzed. Cell proliferation, apoptosis and metastasis were monitored by cell counting kit-8 (CCK-8), flow cytometry, and Transwell assay. The dual-luciferase reporter gene assay and RIP assay were employed to verify the targeting relationship between circ_0000527 and miR-646, miR-646 and LRP6. Results: Circ_0000527 was highly expressed in both RB and RB cell lines, whose high expression level and degree of differentiation were significantly correlated with the increase in cTNM staging level. Overexpression of circ_0000527 contributed to RB cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000527 inhibited the above malignant biological behavior. The underlying mechanism suggested that functioning as a endogenous competitive RNA, circ_0000527 directly targeted miR-646 and positively regulated LRP6 expression. Conclusion: Circ_0000527 enhances the proliferation and metastasis of RB cells by modulating the miR-646/LRP6 axis.

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Section: Discussionmentioning

confidence: 99%

“…MiRNAs are also reported to be engaged in the regulation of the tumorigenesis and progression of a variety of human tumors [ 25 , 26 ]. MiR-646 is regarded as a tumor suppressor in many human cancers.…”

Section: Discussionmentioning

confidence: 99%

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Zhang¹,

Wu²,

Li³

et al. 2020

Cancer Cell Int

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“…Exosomes are emerging as new circulating biomarkers in the liquid biopsy field. Cell membrane-derived nanovesicles (30–100 nM in diameter), containing RNA, microRNA, lipids and proteins, exosomes are released by several cell types and mainly by tumor cells [ 9 , 87 , 88 ]. The possibility to isolate exosomes from different sources, as well as to monitor their content in a relatively simple way, allows one to follow tumor evolution and evaluate the response to therapy over time.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Galardi

Colletti

Lavarello

et al. 2020

Cancers

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Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.

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“…The various roles played by miRNA in neoplasia have been continuously reported and confirmed [109]. Their potential use as circulating biomarkers has been widely speculated, either as cell-free miRNA or when included as vesicle cargo [110][111][112].…”

Section: Small-ev Cargo As Disease Markersmentioning

confidence: 92%

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Bernardi

Farina

2021

Biology

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Extracellular vesicles (exosomes, in particular) are essential in multicellular organisms because they mediate cell-to-cell communication via the transfer of secreted molecules. They are able to shuttle different cargo, from nucleic acids to proteins. The role of exosomes has been widely investigated in solid tumors, which gave us surprising results about their potential involvement in pathogenesis and created an opening for liquid biopsies. Less is known about exosomes in oncohematology, particularly concerning the malignancies deriving from myeloid lineage. In this review, we aim to present an overview of immunomodulation and the microenvironment alteration mediated by exosomes released by malicious myeloid cells. Afterwards, we review the studies reporting the use of exosomes as disease biomarkers and their influence in response to treatment, together with the recent experiences that have focused on the use of exosomes as therapeutic tools. The further development of new technologies and the increased knowledge of biological (exosomes) and clinical (myeloid neoplasia) aspects are expected to change the future approaches to these malignancies.

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Exosomal MiRNAs in Pediatric Cancers

Cited by 45 publications

References 146 publications

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

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