EWI‐2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis

Fu, Chenying; Zhang, Qing; Wang, Ani; Yang, Songpeng; Jiang, Yangfu; Bai, Lin; Quan, Wei

doi:10.1002/1878-0261.12930

Cited by 19 publications

(10 citation statements)

References 78 publications

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“…Studies have shown that specific miRNAs delivered by exosomes can affect the function of cocultured cells ( 19 , 37 ). These results indicate that miRNAs in plasma exosomes can be transported to recipient cells through exosomes and then regulate functions of cells, although the parental cells of plasma exosomes selected in this study are not clear.…”

Section: Discussionmentioning

confidence: 99%

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy

et al. 2022

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Graves ophthalmopathy (GO), a manifestation of Graves’ disease, is an organ-specific autoimmune disease. Intravenous glucocorticoid therapy (ivGCs) is the first-line treatment for moderate-to-severe and active GO. However, ivGCs is only effective in 70%–80% of GO patients. Insensitive patients who choose 12-week ivGCs not only were delayed in treatment but also took the risk of adverse reactions of glucocorticoids. At present, there is still a lack of effective indicators to predict the therapeutic effect of ivGCs. Therefore, the purpose of this study is to find biomarkers that can determine the sensitivity of ivGCs before the formulation of treatment, and to clarify the mechanism of its regulation of ivGCs sensitivity. This study first characterized the miRNA profiles of plasma exosomes by miRNA sequencing to identify miRNAs differentially expressed between GO patients with significant improvement (SI) and non-significant improvement (NSI) after ivGCs treatment. Subsequently, we analyzed the function of the predicted target genes of differential miRNAs. According to the function of the target genes, we screened 10 differentially expressed miRNAs. An expanded cohort verification showed that compared with NSI patients, mir-885-3p was upregulated and mir-4474-3p and mir-615-3p were downregulated in the exosomes of SI patients. Based on statistical difference and miRNA function, mir-885-3p was selected for follow-up study. The in vitro functional analysis of exosomes mir-885-3p showed that exosomes from SI patients (SI-exo) could transfer mir-885-3p to orbital fibroblasts (OFs), upregulate the GRE luciferase reporter gene plasmid activity and the level of glucocorticoid receptor (GR), downregulate the level of inflammatory factors, and improve the glucocorticoid sensitivity of OFs. Moreover, these effects can be inhibited by the corresponding miR inhibitor. In addition, we found that high levels of mir-885-3p could inhibit the AKT/NFκB signaling pathway, upregulate the GRE plasmid activity and GR level, and downregulate the level of inflammatory factors of OFs. Moreover, the improvement of glucocorticoid sensitivity by mir-885-3p transmitted by SI-exo can also be inhibited by the AKT/NFκB agonist. Finally, through the in vivo experiment of the GO mouse model, we further determined the relationship between exosomes’ mir-885-3p sequence, AKT/NFκB signaling pathway, and glucocorticoid sensitivity. As a conclusion, plasma exosomes deliver mir-885-3p and inhibit the AKT/NFκB signaling pathway to improve the glucocorticoid sensitivity of OFs. Exosome mir-885-3p can be used as a biomarker to determine the sensitivity of ivGCs in GO patients.

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Section: Discussionmentioning

confidence: 99%

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy

et al. 2022

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“…According to the role of exosomes in influencing cancer progression, a significant attempt has been made to reveal the role of exosomes in clinical background [504][505][506][507][508]. The genes contained in exosomes can be considered as biomarkers for the diagnosis of lung cancer.…”

Section: Clinical Application and Role Of Exosomes As Biomarkersmentioning

confidence: 99%

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

et al. 2022

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Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract

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“…In addition to RBPs, other proteins or lipids have been reported to participate in miRNA sorting. Most recently, EWI-2 was found to be enriched in EVs and regulate the sorting of multiple miRNAs into EVs [ 32 ]. EWI-2 is a member of the Ig protein subfamily that functions as a TGFβ signal inhibitor and regulates cancer cell proliferation and metastasis [ 33 ].…”

Section: Noncoding Rna Sorting Into Evsmentioning

confidence: 99%

“…EWI-2 is a member of the Ig protein subfamily that functions as a TGFβ signal inhibitor and regulates cancer cell proliferation and metastasis [ 33 ]. EWI-2 is localized on both plasma membranes and the nuclear envelope, and the EWI-2 knockout enforces miR-3934–5p packaging into sEVs and targets EGFR signaling [ 32 ]. Interestingly, the cytoplasmic tail of EWI-2 actively engages with the cell membrane via phosphatidylinositol phosphate (PIP) binding and palmitoylation [ 34 ], suggesting that membrane lipids could mediate RNA sorting.…”

Section: Noncoding Rna Sorting Into Evsmentioning

confidence: 99%

Noncoding RNAs from tissue-derived small extracellular vesicles: Roles in diabetes and diabetic complications

Chang

Lin

et al. 2022

Molecular Metabolism

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EWI‐2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis

Cited by 19 publications

References 78 publications

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy

Plasma Exosomes Transfer miR-885-3p Targeting the AKT/NFκB Signaling Pathway to Improve the Sensitivity of Intravenous Glucocorticoid Therapy Against Graves Ophthalmopathy

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Noncoding RNAs from tissue-derived small extracellular vesicles: Roles in diabetes and diabetic complications

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