Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer

Zaharie, Florin; Petrushev, Bobe; Berce, Cristian; Gafencu, Grigore; Selicean, Sonia; Jurj, Ancuța; Cojocneanu, Roxana; Lisencu, Cosmin-Ioan; Pop, Laura; Pileczki, Valentina; Eniu, Dan; Muresan, Mihai-Stefan; Zaharie, Roxana; Berindan‐Neagoe, Ioana; Tomuleasa, Ciprian; Irimie, Alexandru

doi:10.15403/jgld.2014.1121.244.375

Cited by 83 publications

(55 citation statements)

References 55 publications

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“…Inducing apoptosis in tumor cells is believed to be a common strategy to fight against cancer (32). Other laboratories have provided evidence that exosomes or MVs could promote apoptosis in tumor cells (33,34). Our data showed that MVs induced autophagy and excessive autophagy might induce apoptosis, which explained in part the inhibitory effect of MVs on leukemia cells.…”

Section: Discussionsupporting

confidence: 55%

Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibit proliferation of leukemia cells

Chen

et al. 2017

Oncology Reports

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Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay. The expression of proteins Bcl-2 and Bax were estimated by western blotting. Transmission electron microscope and western blot analysis were adopted to evaluate the autophagy level. Results showed that both hESC‑MSCs and hESC‑MSC‑MVs inhibited proliferation of leukemia cells in a concentration-dependent manner. hESC‑MSC‑MVs reduced the ratio of Bcl/Bax, enhanced the protein level of Beclin-1 and LC3-II conversion, thus upregulating autophagy and apoptosis. In conclusion, microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibited tumor growth and stimulated autophagy and excessive autophagy might induce apoptosis.

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Section: Discussionsupporting

confidence: 55%

Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibit proliferation of leukemia cells

Chen

et al. 2017

Oncology Reports

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“…MicroRNAs (miRNAs/miRs) are small, endogenous, non-coding RNAs composed of 18–25 nucleotides that regulate gene expression at the post-transcriptional level (1). Certain miRNAs act as oncogenes or tumor suppressors and are considered to be among the key regulators of cancer progression (2,3).…”

Section: Introductionmentioning

confidence: 99%

miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

et al. 2017

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MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)-A*2402-restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA-A*2402-matched group and 10 patients from the HLA-A*2402-unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402-matched group with high expression of miR-196b-5p and low expression of miR-378a-3p and miR-486-5p. There was no difference in prognosis in the 10 patients in the HLA-A*2402-unmatched group. Therefore, high miR-196b expression and low miR-378a-3p and miR-486-5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR-196b-5p, miR-378a-3p and miR-486-5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination.

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“…Furthermore, miR-379 in CRC-derived exosomes has been found to down-regulate the migration of CRC cells, and transfer of these engineered miR-379-overexpressing exosomes to recipient cells reduced their migration [101]. Similarly, Zaharie et al have demonstrated that exosomal microRNA-375 inhibits tumor cell dissemination by blocking Bcl-2 in colon cancer, suggesting that exosomal microRNA-375 can be considered a potential therapeutic target [102]. Furthermore, it has been suggested since there is a positive correlation between exosomal miR-193a expression and liver metastasis of colon cancer, the major vault protein (MVP) can possibly decrease the level of circulating exosomal miR-193a, providing a new therapeutic approach for metastatic colon cancer [103].…”

Section: Exosomal Mirnasmentioning

confidence: 98%

Emerging roles and therapeutic value of exosomes in cancer metastasis

Wang

et al. 2019

Mol Cancer

114

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Exosomes are cell-derived vesicles of 30 to 150 nm that contain diverse proteins, nucleic acids, and lipids. These vesicles facilitate effective intercellular communication and trigger profound environmental changes. In recent years, many studies have identified diverse roles for exosomes in tumor metastasis, a major cause of cancer-related deaths; furthermore, circulating tumor-derived exosomes can drive the initiation and progression of metastasis and determine the specific target organs affected. Fortunately, our growing understanding of exosomes and relevant modification technology have provided new ideas for potential treatment of tumor metastases. Here we review recent advances concerning the role of exosomes in metastasis, focusing on their regulatory mechanisms and therapeutic targeting in advanced cancer.

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Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer

Abstract: The present study brings to the forefront new data that suggest miR-375 as a new player in controlling the pathways responsible for inhibiting the natural history of CRC tumor cells, via the Bcl-2 pathway.

Cited by 83 publications

References 55 publications

Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibit proliferation of leukemia cells

Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibit proliferation of leukemia cells

miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Emerging roles and therapeutic value of exosomes in cancer metastasis

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