Cancer-Derived Extracellular Vesicle-Associated MicroRNAs in Intercellular Communication: One Cell’s Trash Is Another Cell’s Treasure

Mills, Joseph; Capece, Marina; Cocucci, Emanuele; Tessari, Anna; Palmieri, Dario

doi:10.3390/ijms20246109

Cited by 52 publications

(43 citation statements)

References 203 publications

(226 reference statements)

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“…Moreover, it was widely demonstrated that the cargo of Extracellular Vesicles (EVs), of which exosomes are the most studied, are enriched with miRNAs which play crucial roles in cancer diagnostics, prognosis and also therapeutic approaches [321,322]. Although clinical application of EV-associated miRNAs is still in its infancy, several studies have demonstrated their potential role in preclinical cancer models [321]. For example, the exomiRNA cytotoxic signal delivered from NK to tumor cells was shown to reduce tumor growth [321].…”

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

“…Although clinical application of EV-associated miRNAs is still in its infancy, several studies have demonstrated their potential role in preclinical cancer models [321]. For example, the exomiRNA cytotoxic signal delivered from NK to tumor cells was shown to reduce tumor growth [321]. Recently, Neviani et al showed that NK-mediated killing of neuroblastoma cells is, at least partly, mediated by the transfer of miR-186 in EVs [321,323].…”

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

“…For example, the exomiRNA cytotoxic signal delivered from NK to tumor cells was shown to reduce tumor growth [321]. Recently, Neviani et al showed that NK-mediated killing of neuroblastoma cells is, at least partly, mediated by the transfer of miR-186 in EVs [321,323]. Moreover, in this study, in vivo activity of miR-186-loaded anionic lipopolyplex nanoparticles directed against neuroblastoma cells through their coating with anti-GD2, a neuroblastoma marker, was proven to be sufficient [321].…”

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

“…Recently, Neviani et al showed that NK-mediated killing of neuroblastoma cells is, at least partly, mediated by the transfer of miR-186 in EVs [321,323]. Moreover, in this study, in vivo activity of miR-186-loaded anionic lipopolyplex nanoparticles directed against neuroblastoma cells through their coating with anti-GD2, a neuroblastoma marker, was proven to be sufficient [321]. Furthermore, the first clinical trials were performed evaluating the potential of miRNA delivery by EVs.…”

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

“…Furthermore, the first clinical trials were performed evaluating the potential of miRNA delivery by EVs. The first phase I trial of a liposomal miR-34a mimic, namely MRX34, was performed in HCC patients and has been published in 2017 [321,324]. Furthermore, miRNA-loaded minicells-called TargomiRs-were used in patients (phase I trial) with recurrent malignant pleural mesothelioma [325].…”

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

See 4 more Smart Citations

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Linck-Paulus

Hellerbrand

Bosserhoff

et al. 2020

Cells

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In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

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Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

Section: Delivery Strategies Of Mirna-associated Therapeuticsmentioning

confidence: 99%

See 3 more Smart Citations

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Linck-Paulus

Hellerbrand

Bosserhoff

et al. 2020

Cells

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Quantitative and Multiplex Detection of Extracellular Vesicle‐Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles

Sulaiman

Juthani

Doyle

2022

Adv Healthcare Materials

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Extracellular vesicle‐derived microRNA (EV‐miRNA) represent a promising cancer biomarker for disease diagnosis and monitoring. However, existing techniques to detect EV‐miRNA rely on complex, bias‐prone strategies, and preprocessing steps, making absolute quantification highly challenging. This work demonstrates the development and application of a method for quantitative and multiplex detection of EV‐miRNA, via rolling circle amplification within encoded hydrogel particles. By a one‐pot extracellular vesicle lysis and microRNA capture step, the bias and losses associated with standard RNA extraction techniques is avoided. The system offers a large dynamic range (3 orders of magnitude), ease of multiplexing, and a limit of detection down to 2.3 zmol (46 × 10−18 m), demonstrating its utility in clinical applications based on liquid biopsy tests. Furthermore, orthogonal measurements of EV concentrations coupled with the direct, absolute quantification of miRNA in biological samples results in quantitative measurements of miRNA copy numbers per volume sample, and per extracellular vesicle.

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Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine‐needle aspiration samples

Ciarletto¹,

Narick²,

Malchoff

et al. 2020

Cancer Cytopathology

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BACKGROUND: Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine-needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one-half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy. In the current study, the authors hypothesized that differential pairwise (diff-pair) analysis of miRNA expression levels would reliably identify MTC in FNA samples. METHODS: The relative abundance of 10 different miRNAs in total nucleic acids was obtained from ThyraMIR test results. Diff-pair analysis was performed by subtracting the critical threshold value of one miRNA from the critical threshold values of other miRNAs. Next-generation sequencing with the ThyGeNEXT panel identified oncogenic gene alterations. The discovery cohort consisted of 30 formalin-fixed, paraffin-embedded benign and malignant thyroid neoplasms, including 4 cases of MTC. After analytical validation, clinical validation was performed using 3 distinct cohorts (total of 7557 specimens). RESULTS: In the discovery cohort, 9 diff-pairs were identified as having significant power using the Kruskal-Wallis test (P < .0001) to distinguish MTC samples from non-MTC samples. The assay correctly classified all MTC and non-MTC samples in the analytical validation study and in the 3 clinical validation cohorts. The overall test accuracy was 100% (95% confidence interval, 99%-100%). In indeterminate FNAC samples, the sensitivity of the diff-pair analysis was greater than that of the MTC-specific mutation analysis (100% vs 25%; P = .03). CONCLUSIONS: Pairwise miRNA expression analysis of ThyraMIR results were found to accurately predict MTC in thyroid FNA samples, including those with indeterminate FNAC findings.

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Cancer-Derived Extracellular Vesicle-Associated MicroRNAs in Intercellular Communication: One Cell’s Trash Is Another Cell’s Treasure

Cited by 52 publications

References 203 publications

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Quantitative and Multiplex Detection of Extracellular Vesicle‐Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles

Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine‐needle aspiration samples

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