miR-1289 and “Zipcode”-like Sequence Enrich mRNAs in Microvesicles

Bolukbasi, Mehmet Fatih; Mizrak, Arda; Ozdener, Gokhan Baris; Madlener, Sibylle; Ströbel, Thomas; Erkan, Erdoğan Pekcan; Fan, Jian‐Bing; Breakefield, Xandra O.; Saydam, Okay

doi:10.1038/mtna.2011.2

Cited by 251 publications

(220 citation statements)

References 41 publications

(59 reference statements)

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“…The molecular mechanism by which nucleic acids are uploaded into exosomes is emerging. A recent study suggests that mRNA sorting into glioblastoma-derived MVs may be directed through the interaction between a "zipcode"-like sequence, present in the transcripts, and miR-1289 [40].…”

Section: Discussionmentioning

confidence: 99%

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

Garzetti¹,

Menon²,

Finardi³

et al. 2013

Journal of Leukocyte Biology

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MVs are known vehicles of horizontal communication among cells, currently under scrutiny as powerful biomarkers in several pathological processes. The potential advantage of MVs relies on the assumption that their content reflects processes ongoing in pathologically relevant cell types. We have described that MVs of myeloid origin in the CSF are a marker of microglia/ macrophage activation. Myeloid cells have different activation types, resulting in diverse functional phenotypes. Knowledge on the activation type of myeloid cells during disease would be of paramount importance for the understanding of ongoing pathogenic processes. We show here that macrophages activated in vitro in different ways all release increased amounts of MVs compared with NS cells. Moreover, we show that macrophage-derived MVs contain a repertoire of mRNAs that is not the result of casual sampling from the parental cells, as it is characterized by distinct mRNA enrichments and species. Nevertheless, mRNA content of MVs clearly allows identification in vivo of the activated phenotype of the cell of origin, indicating carryover of functional macrophage traits. We propose that detection of mRNAs in myeloid MVs permits identification of myeloid cell activation type during disease, allowing for further stratification of pathological processes. J. Leukoc. Biol. 95: 817-825; 2014.

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Section: Discussionmentioning

confidence: 99%

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

Garzetti¹,

Menon²,

Finardi³

et al. 2013

Journal of Leukocyte Biology

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“…Interestingly, vesiculation is known to lead to selective enrichment of some bioactive molecules but not others in the EV cargo, and the nature, mechanisms and consequences of these combinatorial processes encompassing large numbers of molecular species involved are still poorly understood [21,31,32].…”

Section: Introductionmentioning

confidence: 99%

Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state

Garnier

Magnus

Meehan

et al. 2013

Experimental Cell Research

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Transitions of the cancer cell phenotype between epithelial and mesenchymal states is likely to alter the patterns of intercellular communication. In this regard we have previously documented that EMT-like changes trigger quantitative changes in exosomal vesicle emission in A431 cancer cells driven by oncogenic epidermal growth factor receptor (EGFR). Here we report that extracellular vesicles (EVs) produced by these cancer cells in their epithelial and mesenchymal states exhibit profound qualitative differences in their proteome. Thus, induction of the EMT-like state through blockade of E-cadherin and EGFR stimulation resulted in mesenchymal shift in cellular morphology and enrichment in the CD44-high/CD24-low immunophenotype, often linked to cellular stemness. This change also resulted in reprogramming of the EV-related proteome (distinct from that of corresponding cells), which contained 30 unique protein signals, and revealed enrichment in pathways related to cellular growth, cell-to-cell signalling, and cell movement. Some of the most prominent EV-related proteins were validated, including integrin "2 and tetraspanin CD9. We propose that changes in cellular differentiation status translate into unique qualitative rearrangements in the cargo of EVs, a process that may have implications for intercellular communication and could serve as source of new biomarkers of EMT-like changes in cancer.3

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“…t-RNA, Y-RNA, vault RNA, etc.) are enriched or underrepresented in EVs compared to their respective parent cells [36][37][38][39][40][41]. Based on these observations it is generally accepted that the composition of EVs is, at least partially, actively regulated by the parent cell [42], albeit that the mechanisms and associated key players regulating this cargo sorting remain largely elusive to date [38,[43][44][45][46].…”

Section: Biogenesis Cargo Loading and Compositionmentioning

confidence: 99%

“…This enrichment could even be further enhanced when miR-1289 was overexpressed in the producing cell [39]. Regarding miRNA sorting, Koppers-lalic et al discovered that 3'-uridylated miRNAs are enriched in human B cell-derived EVs [45].…”

Section: Loading Evs With a Therapeutic Cargomentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

156

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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miR-1289 and “Zipcode”-like Sequence Enrich mRNAs in Microvesicles

Cited by 251 publications

References 41 publications

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

Activated macrophages release microvesicles containing polarized M1 or M2 mRNAs

Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state

Therapeutic and diagnostic applications of extracellular vesicles

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