Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells

Song, Man; Wang, Yu; Shang, Zhiguo; Liu, Xiao Dan; Xie, Da; Wang, Qi; Guan, Hua; Zhou, Ping‐Kun

doi:10.1038/srep30165

Cited by 67 publications

(80 citation statements)

References 55 publications

(70 reference statements)

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“…One other miRNA, miR-7, is noteworthy because it has previously been detected in exosomes derived from irradiated bronchial epithelial cells and linked directly to propagation of radiation-induced bystander effect in recipient cells (Song et al, 2016). Autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 98%

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

Dynan

Jaafar

et al. 2020

Preprint

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Exosomes are extracellular vesicles that mediate transport of nucleic acids, proteins, and other molecules. Prior work has implicated exosomes in the transmission of radiation nontargeted effects. Here we investigate the ability of energetic heavy ions, representative of species found in galactic cosmic rays, to stimulate exosome release from human bronchial epithelial cells in vitro. Immortalized human bronchial epithelial cells (HBEC3-KT F25F) were irradiated with 1.0 Gy of high linear energy transfer (LET) 48Ti, 28Si, or 16O ions, or with 10 Gy of low-LET reference γ-rays, and extracellular vesicles were collected from conditioned media. Preparations were characterized by single particle tracking analysis, transmission electron microscopy, and immunoblotting for the exosomal marker, TSG101. Irradiation with high-LET ions, but not γ-rays, stimulated exosome release by about 3-fold, relative to mock-irradiated controls. The exosome-enriched vesicle preparations contained pro-inflammatory damage-associated molecular patterns, including HSP70 and calreticulin. Additionally, miRNA profiling was performed for vesicular RNAs using NanoString technology. The miRNA profile was skewed toward a small number of species that have previously been shown to be involved in cancer initiation and progression, including miR-1246, miR-1290, miR-23a, and miR-205. Additionally, a set of 24 miRNAs was defined as modestly over-represented in preparations from HZE ion-irradiated versus other cells. Gene set enrichment analysis based on the over-represented miRNAs showed highly significant association with nonsmall cell lung and other cancers.

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Section: Discussionmentioning

confidence: 98%

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

Dynan

Jaafar

et al. 2020

Preprint

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“…These results may be interpreted that MEG3 acted as a sponge of miR-7-5p to regulate the activation of downstream mTOR signalling, and in turn, modulate cardiomyocytes autophagy. MiR-7-5P is an important regulator in cell autophagy in various cell type [55][56][57].…”

Section: Discussionmentioning

confidence: 99%

Uric acid and sphingomyelin enhance autophagy in iPS cell-originated cardiomyocytes through lncRNA MEG3/miR-7-5p/EGFR axis

Cao

Wen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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2019) Uric acid and sphingomyelin enhance autophagy in iPS cell-originated cardiomyocytes through lncRNA MEG3/miR-7-5p/EGFR axis, Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 3774-3785, ABSTRACTThis study aimed to determine the metabolites associated with ventricular septal defect (VSD) and the underlying mechanisms. Blood samples and thymus tissues were collected from VSD patients to perform LC-MS-based metabolomics assay and generate iPS cell-derived cardiomyocytes, respectively. VSD rat model was used in vivo study. RT-PCR, western blotting, immunohistochemistry, luciferase activity assay, GFP-LC3 adenovirus and GFP and RFP tfLC3 assay, and transmission electron microscopy were performed to investigate the underlying mechanisms. The metabolites uric acid (UA) and sphingomyelin (SM) increased in the serum of VSD patients, along with enhanced autophagy. The combination of UA and SM treatment could promote autophagy and inhibit EGFR and AKT3 expressions. Overexpression of EGFR and AKT3 suppressed autophagy in UA and SM-treated cardiomyocytes, respectively. Also, lncRNA MEG3 knockdown and overexpression could enhance and inhibit autophagy in UA and SM-treated cardiomyocytes, respectively, through targeting miR-7-5p. Moreover, miR-7-5p mimics and inhibitors promoted and inhibited autophagy in UA and SM-treated cardiomyocytes, respectively, via target EGFR. In VSD rat model, upregulation of MEG3 could reverse high level of autophagy and decrease serum UA and SM. In conclusion, UA and SM are essential VSD-associated metabolic biomarkers and MEG3/miR-7-5p/EGFR axis is critical to the regulation of autophagy in cardiomyocytes. ARTICLE HISTORY

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“…We and other colleagues have shown that the increase in basal autophagy accompanies the development of cisplatin resistance in NSCLC cells and that inhibiting basal autophagy sensitizes NSCLC cells to cisplatin-induced apoptosis (17)(18)(19). In addition, previous studies show that exosomal miRNAs are able to regulate autophagy in recipient cells by targeting autophagyrelated genes (20)(21)(22). These findings have driven us to investigate the prognostically relevant correlation between basal autophagy contributing to treatment responsiveness and miRNAs derived from circulating exosomes in patients with NSCLC.…”

Section: Introductionmentioning

confidence: 94%

Prognostic Role of Circulating Exosomal miR-425-3p for the Response of NSCLC to Platinum-Based Chemotherapy

Yuwen

Wang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Platinum-based doublets with a third-generation agent are the recommended option for many patients with non-small cell lung cancer (NSCLC) with no contraindications to platinum compounds. Unfortunately, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. Circulating exosomal miRNAs were isolated and used to perform HiSeq deep-sequencing analyses on serum pool samples from platinum-resistant or platinum-sensitive patients, and six exosomal miRNAs were further validated for their predictive utility by qRT-PCR in 170 serum samples of patients with advanced NSCLC. Gain- and loss-of-function experiments clarified the responsiveness regulating role of the clinically relevant miRNA. IHC analyses were performed to evaluate the association between basal autophagy in lung cancer tissues and responsiveness in 203 patients with NSCLC receiving platinum-based chemotherapy. Six circulating exosomal miRNAs (miR-425-3p, miR-1273h, miR-4755-5p, miR-9-5p, miR-146a-5p, and miR-215-5p) were found to be differentially expressed with the largest fold change in platinum-resistant patients compared with platinum-sensitive patients. High miR-425-3p proved to be a potent predictive biomarker for low responsiveness and poor progression-free survival (PFS). Mechanistically, miR-425-3p upregulated the autophagic levels via targeting AKT1, leading to the decrease in therapeutic response. Concordantly, high levels of basal autophagy in lung cancer tissues correlate with low responsiveness in patients with NSCLC within the early and advanced disease stages. Our study highlights circulating exosomal miR-425-3p as a potential biomarker for improved predictions of the clinical response to platinum-based chemotherapy in patients with NSCLC. This study provides the first evidence that miR-425-3p in NSCLC patient-derived exosomes can be a marker for predicating the clinical response to platinum-based chemotherapy.

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Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells

Cited by 67 publications

References 55 publications

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

Uric acid and sphingomyelin enhance autophagy in iPS cell-originated cardiomyocytes through lncRNA MEG3/miR-7-5p/EGFR axis

Prognostic Role of Circulating Exosomal miR-425-3p for the Response of NSCLC to Platinum-Based Chemotherapy

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