Exosome-mediated delivery of functionally active miRNA-375-3p mimic regulate epithelial mesenchymal transition (EMT) of colon cancer cells

Rezaei, Ramazan; Baghaei, Kaveh; Amani, Davar; Piccin, Andrea; Hashemi, Seyed Mahmoud; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

doi:10.1016/j.lfs.2021.119035

Cited by 51 publications

(41 citation statements)

References 58 publications

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“…It has been reported that tumor-derived exosomes play important roles in tumorigenesis ( Rezaei et al, 2021 ; Xie et al, 2021 ). Thus, we sought to isolate the exosomes from A549 cells, and then exosomes isolation was detected by TEM.…”

Section: Resultsmentioning

confidence: 99%

Tumor Cell-Derived Exosomal miR-770 Inhibits M2 Macrophage Polarization via Targeting MAP3K1 to Inhibit the Invasion of Non-small Cell Lung Cancer Cells

Liu

Luo

Wang

et al. 2021

Front. Cell Dev. Biol.

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BackgroundNon-small cell lung carcinoma (NSCLC) is a type lung cancer with high malignant behaviors. MicroRNAs (miRNAs) are known to be involved in progression of NSCLC. In order to explore potential targets for the treatment of NSCLC, bioinformatics tool was used to analyze differential expressed miRNAs between NSCLC and adjacent normal tissues.MethodsBioinformatics tool was used to find potential targets for NSCLC. Cell proliferation was investigated by Ki67 staining. Cell apoptosis was measured by flow cytometry. mRNA and protein expression in NSCLC cells were detected by RT-qPCR and Western-blot, respectively. Transwell assay was performed to test the cell migration and invasion. In order to investigate the function of exosomal miRNA in NSCLC, in vivo model of NSCLC was constructed.ResultsMiR-770 was identified to be downregulated in NSCLC, and miR-770 agomir could significantly inhibit NSCLC cell proliferation through inducing the apoptosis. Additionally, the metastasis of NSCLC cells was decreased by miR-770 agomir. MAP3K1 was identified to be the target mRNA of miR-770. Meanwhile, tumor cell-derived exosomal miR-770 inhibited M2 macrophage polarization via downregulation of MAP3K1, which in turn suppressed NSCLC cell invasion. Besides, tumor cell-derived exosomal miR-770 markedly decreased NSCLC tumor growth in vivo through suppressing M2 macrophage polarization.ConclusionTumor cell-derived exosomal miR-770 inhibits M2 macrophage polarization to inhibit the invasion of NSCLC cells via targeting MAP3K1. Thus, this study provided a new strategy for the treatment of NSCLC.

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Section: Resultsmentioning

confidence: 99%

Tumor Cell-Derived Exosomal miR-770 Inhibits M2 Macrophage Polarization via Targeting MAP3K1 to Inhibit the Invasion of Non-small Cell Lung Cancer Cells

Liu

Luo

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…The Smad7 gene needs the help of a gene vector with high biocompatibility and good targeting property to enter into the cells. Exosomes are small vesicles with a diameter of 30-150 nm naturally secreted by cells [ 33 ], and they can be used as potential carriers to deliver drugs, therapeutic genes or proteins in clinical treatment due to their stability and high biocompatibility [ 34 – 37 ]. In current study, the exosomes produced from mouse aortic endothelial cells were selected as vehicles of gene therapy as it mirror the marker molecules of parent cells and was associated with many physiological progresses such as anti-inflammation, anti-oxidation and the inhibition of endothelial-to-mesenchymal transition (EndMT) [ 12 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Wei

Yang

Hsu

et al. 2021

BMC Musculoskelet Disord

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Background Heterotopic ossification (HO) can limit joint activity, causes ankylosis and impairs the function and rehabilitation of patients. Endothelial to mesenchymal transition (EndMT) plays an important role in the pathogenesis of HO, and high expression of SMAD7(Mothers Against Decapentaplegic Homolog 7) in endothelial cells can effectively reverse the TGF-β1 mediated EndMT. This article studied an appropriately engineered exosome with high biocompatibility and good targeting property to administrate SMAD7 gene therapy to inhibit the EndMT. Methods Exosomes from mouse aortic endothelial cells were cultured and harvested. DSPE-PEG and antibody CD34 were combined to exosomes to synthesize the endothelial cell targeting exosome vector (Exosome-DSPE-PEG-AbCD34). The biocompatibility, stability, targeting and cell internalization of exosome vector were tested, then the Exosome-DSPE-PEG-AbCD34 was loaded with Smad7 plasmid and administrated to MAECs to examine its therapeutic effect on EndMT of MAEC mediated by TGF-β1. Results The Exosome-DSPE-PEG-AbCD34 has no impact on MAEC cell viability at high concentration, and exosome-DSPE-PEG-AbCD34 could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-AbCD34 has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-AbCD34-Smad7 could significantly increase the level of SMAD7, decrease the expression of TGF-β1, and effectively reverse the EndMT of MAEC mediated by TGF- β1 in MAEC cells. Conclusions The synthesized Exosome-DSPE-PEG-AbCD34-Smad7 has good biological properties and can effectively reverse the EndMT of MAEC mediated by TGF-β1. Thus, Exosome-DSPE-PEG-AbCD34-Smad7 may has the potential for the prevention and treatment of HO.

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“…Interestingly, miR-375 mimicThe tumor-derived exosome containing miR-375 mimic that could inhibit the EMT process. 94 According to Fu et al 95 the high expression of miR-17-5p and miR-92a-3p were consistent with the tumorigenesis and metastasis of CRC by exploring serum exosomal miRNAs levels of normal controls and CRC patients. Interestingly, exosomal miR-1246/92b-3p/27a-3p derived by fusobacterium nucleatum-infected CRC cells facilitate uninfected cells metastasis.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Colorectal liver metastasis: molecular mechanism and interventional therapy

Zhou

Liu

Wang

et al. 2022

Sig Transduct Target Ther

140

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Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

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Exosome-mediated delivery of functionally active miRNA-375-3p mimic regulate epithelial mesenchymal transition (EMT) of colon cancer cells

Cited by 51 publications

References 58 publications

Tumor Cell-Derived Exosomal miR-770 Inhibits M2 Macrophage Polarization via Targeting MAP3K1 to Inhibit the Invasion of Non-small Cell Lung Cancer Cells

Tumor Cell-Derived Exosomal miR-770 Inhibits M2 Macrophage Polarization via Targeting MAP3K1 to Inhibit the Invasion of Non-small Cell Lung Cancer Cells

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

Colorectal liver metastasis: molecular mechanism and interventional therapy

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