Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression

Ding, Yixuan; Cao, Feng; Sun, Haiyan; Wang, Yecheng; Liu, Shuang; Wu, Yali; Cui, Qingye; Mei, Wentong; Li, Fēi

doi:10.1016/j.canlet.2018.10.039

Cited by 126 publications

(86 citation statements)

References 37 publications

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“…These results suggest a role for miRNA in the anti‐inflammatory/regenerative function displayed by the CSSC EVs. Such a function is consistent with a number of recent studies that have linked miRNA delivery by EVs to regenerative, antifibrotic, and immune suppressive properties of the vesicles . Some authors have suggested that the small amount of miRNA in EVs makes it more likely that a protein cargo is involved in their biological properties .…”

Section: Discussionsupporting

confidence: 88%

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

Shojaati

Khandaker

Funderburgh

et al. 2019

Stem Cells Translational Medicine

120

104

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Mesenchymal stem cells from corneal stromal stem cells (CSSC) prevent fibrotic scarring and stimulate regeneration of transparent stromal tissue after corneal wounding in mice. These effects rely on the ability of CSSC to block neutrophil infiltration into the damaged cornea. The current study investigated the hypothesis that tissue regeneration by CSSC is mediated by secreted extracellular vesicles (EVs). CSSC produced EVs 130–150 nm in diameter with surface proteins that include CD63, CD81, and CD9. EVs from CSSC reduced visual scarring in murine corneal wounds as effectively as did live cells, but EVs from human embryonic kidney (HEK)293T cells had no regenerative properties. CSSC EV treatment of wounds decreased expression of fibrotic genes Col3a1 and Acta2, blocked neutrophil infiltration, and restored normal tissue morphology. CSSC EVs labeled with carboxyfluorescein succinimidyl ester dye, rapidly fused with corneal epithelial and stromal cells in culture, transferring microRNA (miRNA) to the target cells. Knockdown of mRNA for Alix, a component of the endosomal sorting complex required for transport, using siRNA, resulted in an 85% reduction of miRNA in the secreted EVs. The EVs with reduced miRNA were ineffective at blocking corneal scarring. Furthermore, CSSC with reduced Alix expression also lost their regenerative function, suggesting EVs as an obligate component in the delivery of miRNA. The results of these studies support an essential role for extracellular vesicles in the process by which CSSC cells block scarring and initiate regeneration of transparent corneal tissue after wounding. EVs appear to serve as a delivery vehicle for miRNA, which affects the regenerative action. Stem Cells Translational Medicine 2019;8:1192–1201

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Section: Discussionsupporting

confidence: 88%

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

Shojaati

Khandaker

Funderburgh

et al. 2019

Stem Cells Translational Medicine

120

104

View full text Add to dashboard Cite

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“…For instance, treating host cells with chemical drugs, such as paclitaxel, can induce the release of exosomes loaded with paclitaxel [ 114 ]. For protein or gene delivery, host cells can be transfected with desired genes, which facilitates the release of exosomes with desired proteins or genes [ 115 ]. Although the endogenous loading method demonstrates a relatively high loading efficiency, it is difficult to quantify the amount of content inside the exosome and maintain high purity.…”

Section: Potential Therapeutic Applications Of Exosomes In Cancermentioning

confidence: 99%

“…Similarly, treatment with miR-379-overexpressing exosomes significantly suppressed tumor growth in a T47D breast tumor model [ 136 ]. In addition, miR-145-5p overexpression inhibited the proliferation of pancreatic ductal adenocarcinoma and induced tumor cell apoptosis in an in vivo model [ 115 ]. In addition, specific miRNA inhibitors could act as potential drug candidates.…”

Section: Potential Therapeutic Applications Of Exosomes In Cancermentioning

confidence: 99%

The Biological Function and Therapeutic Potential of Exosomes in Cancer: Exosomes as Efficient Nanocommunicators for Cancer Therapy

Choi

Park

Lee

et al. 2020

IJMS

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Cancer therapeutics must be delivered to their targets for improving efficacy and reducing toxicity, though they encounter physiological barriers in the tumor microenvironment. They also face limitations associated with genetic instability and dynamic changes of surface proteins in cancer cells. Nanosized exosomes generated from the endosomal compartment, however, transfer their cargo to the recipient cells and mediate the intercellular communication, which affects malignancy progression, tumor immunity, and chemoresistance. In this review, we give an overview of exosomes’ biological aspects and therapeutic potential as diagnostic biomarkers and drug delivery vehicles for oncotherapy. Furthermore, we discuss whether exosomes could contribute to personalized cancer immunotherapy drug design as efficient nanocommunicators.

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“…Previous studies showed that decreased expression of miR-145-5p caused by promoter methylation is a prognostic factor for endometrial cancer, and it suppresses the growth of laryngeal carcinoma by targeting FSCN1 [19,20]. Exosomes delivered miR-145-5p also represses the progression of pancreatic adenocarcinoma and ovarian cancer [21,22]. Moreover, miR-145-5p act as a tumor suppressor in GC by targeting N-cadherin and ZEB2 [23].…”

Section: Introductionmentioning

confidence: 99%

CircDUSP16 promotes the tumorigenesis and invasion of gastric cancer by sponging miR-145-5p

et al. 2019

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Background Circular RNAs (circRNAs) as a novel subgroup of non-coding RNAs act a critical role in the pathogenesis of gastric cancer (GC). However, the underlying mechanisms by which hsa_circ_0003855 (circDUSP16) contributes to GC are still undocumented. Materials The differentially expressed circRNAs were identified by GEO database. The association of circDUSP16 or miR-145-5p expression with clinicopathological features and prognosis in GC patients was analyzed by FISH and TCGA-seq data set. Loss-and gain-of-function experiments as well as a xenograft tumor model were performed to assess the role of circDUSP16 in GC cells. circDUSP16-specific binding with miR-145-5p was confirmed by bioinformatic analysis, luciferase reporter, and RNA immunoprecipitation assays. Results The expression levels of circDUSP16 were markedly increased in GC tissue samples and acted as an independent prognostic factor of poor survival in patients with GC. Knockdown of circDUSP16 repressed the cell viability, colony formation, and invasive potential in vitro and in vivo, but ectopic expression of circDUSP16 reversed these effects. Moreover, circDUSP16 possessed a co-localization with miR-145-5p in the cytoplasm, and acted as a sponge of miR-145-5p, which attenuated circDUSP16-induced tumor-promoting effects and IVNS1ABP expression in GC cells. MiR-145-5p had a negative correlation with circDUSP16 expression and its low expression was associated with poor survival in GC patients. Conclusions CircDUSP16 facilitates the tumorigenesis and invasion of GC cells by sponging miR-145-5p, and may provide a novel therapeutic target for GC.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression

Cited by 126 publications

References 37 publications

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

The Biological Function and Therapeutic Potential of Exosomes in Cancer: Exosomes as Efficient Nanocommunicators for Cancer Therapy

CircDUSP16 promotes the tumorigenesis and invasion of gastric cancer by sponging miR-145-5p

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