MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells

Pakravan, Katayoon; Babashah, Sadegh; Sadeghizadeh, Majid; Mowla, Seyed Javad; Mossahebi-Mohammadi, Majid; Ataei, Farangis; Dana, Nasim; Javan, Mohammad

doi:10.1007/s13402-017-0335-7

Cited by 291 publications

(205 citation statements)

References 66 publications

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“…They realized that miR‐16 which is enriched in MSC‐derived exosomes, target VEGF and through this way affect endothelial cell proliferation. Similarly, in another study Pakravan et al () have shown that MSC‐derived exosomes decrease the expression of VEGF through modulating mTOR/HIF‐1α signaling pathways in breast cancer. They found that MSC‐derived exosomes contain high levels of miR‐100.…”

Section: Scs‐derived Exosomes and Tumor Angiogenesismentioning

confidence: 80%

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

Aslan

Maralbashi

Salari

et al. 2019

Journal Cellular Physiology

110

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Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor‐associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.

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Section: Scs‐derived Exosomes and Tumor Angiogenesismentioning

confidence: 80%

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

Aslan

Maralbashi

Salari

et al. 2019

Journal Cellular Physiology

110

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“…For example, when exosomes were transferred from adriamycin- and docetaxel-tolerant breast cancer-resistant cell lines to the sensitive cell line, some miRNAs (miR-100, miR-222, miR-30a, and miR-17) would generate drug resistance. 17, 28–30 In studies on prostatic cancer and docetaxel resistance, the exosomes secreted by drug-resistant cells can regulate the expression of target cell translocators and endow sensitive cells with docetaxel resistance. 31 According to our research, levels of miRNA193 in esophageal cancer drug-resistant cell line TE-1/DDP and exosome TE-1/DDP/exo significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells

Shi

Huang

et al. 2019

Preprint

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AbstractPurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.

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“…The expression of miRNA was normalized to U6 small nuclear RNA (U6snRNA). The fold changes of gene expression were determined using the 2 −ΔΔCt method (Hayat Nosaeid et al, ; Pakravan et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Down-regulation of the lncRNA H19 and miR-675 during neural differentiation of BMSCs of miRNA was normalized to U6 small nuclear RNA (U6snRNA). The fold changes of gene expression were determined using the 2 ÀDDCt method (Hayat Nosaeid et al, 2009;Pakravan et al, 2017). NSE and MAP-2 proteins were detected by immunocytochemistry (ICC) according to the standard protocol.…”

Section: Quantitative Real-time Pcr and Immunocytochemistrymentioning

confidence: 99%

Down‐regulation of the non‐coding RNA H19 and its derived miR‐675 is concomitant with up‐regulation of insulin‐like growth factor receptor type 1 during neural‐like differentiation of human bone marrow mesenchymal stem cells

Farzi-Molan

Babashah

Bakhshinejad

et al. 2018

Cell Biology International

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The differentiation of human bone marrow mesenchymal stem cells (BMSCs) into specific lineages offers new opportunities to use the therapeutic efficiency of these pluripotent cells in regenerative medicine. Multiple lines of evidence have revealed that non-coding RNAs play major roles in the differentiation of BMSCs into neural cells. Here, we applied a cocktail of neural inducing factors (NIFs) to differentiate BMSCs into neural-like cells. Our data demonstrated that during neurogenic induction, BMSCs obtained a neuron-like morphology. Also, the results of gene expression analysis by qRT-PCR showed progressively increasing expression levels of neuron-specific enolase (NSE) as well as microtubule-associated protein 2 (MAP-2) and immunocytochemical staining detected the expression of these neuron-specific markers along differentiated BMSC bodies and cytoplasmic processes, confirming the differentiation of BMSCs into neuronal lineages. We also compared differences in the expression levels of the long non-coding RNA (lncRNA) H19 and H19-derived miR-675 between undifferentiated and neurally differentiated BMSCs and found that during neural differentiation down-regulation of the lncRNA H19/miR-675 axis is concomitant with up-regulation of insulin-like growth factor type-1 (IGF-1R), a well-established target of miR-675 involved in neurogenesis. The findings of the current study provide support for the hypothesis that miR-675 may confer functionality to H19, suggesting a key role for this miRNA in the neural differentiation of BSMCs. However, further investigation is required to gain deeper insights into the biological roles of this miRNA in the complex process of neurogenesis.

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MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells

Abstract: Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.

Cited by 291 publications

References 66 publications

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells

Down‐regulation of the non‐coding RNA H19 and its derived miR‐675 is concomitant with up‐regulation of insulin‐like growth factor receptor type 1 during neural‐like differentiation of human bone marrow mesenchymal stem cells

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