Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing

Ren, Jia; Zhou, Quan; Li, Hao; Li, Jianfang; Pang, Li; Gu, Qinxuan; Zhu, Zhenggang; Liu, Bingya

doi:10.1177/1010428317695012

Cited by 29 publications

(23 citation statements)

References 36 publications

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“…Our results revealed that the concentration of exosomes derived from MG-infected CP-Ⅱ cells was increased as non-infected cells (Fig. 1E, Table S3),, which was similar to the results of previous reports in other diseases (35,50). Moreover, the presence of protease-rich exosomes in the airway secretions from subjects with cystic fibrosis lung disease colonized by gram-negative bacteria.…”

Section: Discussionsupporting

confidence: 91%

Analysis of deep sequencing Exosome-microRNA expression profile from Chicken Type Ⅱ Pneumocytes derived reveals potential role of gga-miRNA-451 in inflammation

Zhao¹,

Fu²,

M³

et al. 2019

Preprint

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Background: Exosomes are nanosized extracellular vesicles secreted by multiple cells in the body, including those located in the respiratory tract and lungs. They are emerging as important inflammatory mediators and can release their contents, especially microRNAs (miRNAs), to both neighboring and distal cells. Mycoplasma gallisepticum (MG) can target host cell and cause chronic respiratory disease (CRD) in chickens. Although exosomal miRNAs have been demonstrated to produce an important effect on microbial pathogenesis and inflammatory response as crucial regulatory noncoding RNAs, the mechanism by which exosomal miRNAs regulate MG-induced inflammation remains to be elucidated. Methods: the expression of exosome-microRNA derived from MG-infected chicken type Ⅱ pneumocytes (CP-Ⅱ) was screened, and the target genes and function of differentially expressed miRNAs (DEGs) were predicted. To verify the inflammatory functions of exosomal gga-miR-451 via targeting YWHAZ, Western blot, ELISA, and RT-qPCR were used in this study. Results: A total of 722 miRNAs were identified from the two exosomal small RNA (sRNA) libraries, and 279 novel miRNAs were discovered; 30 miRNAs (9 up-regulated and 21 down-regulated) were significantly changed (P＜0.05). Function annotation analysis of DEGs showed that the target miRNAs were significantly enriched in treatment group, such as cell cycle, Toll-like receptor signaling pathway and MAPK signaling pathway, etc. The results have also confirmed that gga-miR-451-absent exosomes derived from MG-infected CP-Ⅱ cells increased inflammatory cytokine production in DF-1 (chicken embryo fibroblast) cells, and Wild Type CP-Ⅱ cells-derived-exosomes displayed protective effects. Conclusion: our work suggests that exosomes from MG-infected CP-Ⅱ cells alter the dynamics of the DF-1 cells, and may contribute to pathology of the MG infection via exosomal gga-miR-451 targeting YWHAZ involving in inflammation. This could potentially be used as a biomarker for diagnostics and treatment.

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Section: Discussionsupporting

confidence: 91%

Analysis of deep sequencing Exosome-microRNA expression profile from Chicken Type Ⅱ Pneumocytes derived reveals potential role of gga-miRNA-451 in inflammation

Zhao¹,

Fu²,

M³

et al. 2019

Preprint

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“…Recent studies have indicated that there are abundant miRNAs encapsulated in exosomes, and these miRNAs play an important role in cell–cell communications 20 . In addition, exosomal miR-21-5p has been proved to be a crucial miRNA in cancer metastasis 21 , 22 , and is enriched in GC-derived exosomes 23 . Therefore, we hypothesized that GC-derived exosomal miR-21-5p mediate MMT activation.…”

Section: Resultsmentioning

confidence: 99%

Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition

et al. 2018

Cell Death Dis

150

110

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Peritoneal metastasis is a primary metastatic route for gastric cancers, and the mechanisms underlying this process are still unclear. Peritoneal mesothelial cells (PMCs) undergo mesothelial-to-mesenchymal transition (MMT) to provide a favorable environment for metastatic cancer cells. In this study, we investigated how the exosomal miR-21-5p induces MMT and promotes peritoneal metastasis. Gastric cancer (GC)-derived exosomes were identified by transmission electron microscopy and western blot analysis, then the uptake of exosomes was confirmed by PKH-67 staining. The expression of miR-21-5p and SMAD7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, and the interactions between miR-21-5p and its target genes SMAD7 were confirmed by Luciferase reporter assays. The MMT of PMCs was determined by invasion assays, adhesion assays, immunofluorescent assay, and western blot. Meanwhile, mouse model of tumor peritoneal dissemination model was performed to investigate the role of exosomal miR-21-5p in peritoneal metastasis in vivo. We found that PMCs could internalize GC-derived exosomal miR-21-5p and led to increased levels of miR-21-5p in PMCs. Through various types of in vitro and in vivo assays, we confirmed that exosomal miR-21-5p was able to induce MMT of PMCs and promote tumor peritoneal metastasis. Moreover, our study revealed that this process was promoted by exosomal miR-21-5p through activating TGF-β/Smad pathway via targeting SMAD7. Altogether, our data suggest that exosomal miR-21-5p induces MMT of PMCs and promote cancer peritoneal dissemination by targeting SMAD7. The exosomal miR-21-5p may be a novel therapeutic target for GC peritoneal metastasis.

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“…In fact, both miRNAs and piRNAs are detectable in human serum, as demonstrated by a recent study based on RNA sequencing analysis in 477 serum samples [104]. Moreover, sncRNAs are enriched in extracellular vesicles (miRNAs ~40%, piRNAs ~40%) [105], allowing for their export from the cell in which they were synthesized to affect cells at a distance [106]. Models based on miRNA and piRNA combinations were able to correctly classify colon and prostate cancer patients from healthy individuals [106].…”

Section: Emerging Roles Of Sncrna As Cancer Biomarkersmentioning

confidence: 93%

Small Noncoding RNA Expression in Cancer

Guisier¹,

Barros-Filho²,

Rock³

et al. 2019

Gene Expression Profiling in Cancer

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Despite an inability to encode proteins, small noncoding RNAs (sncRNAs) have critical functions in the regulation of gene expression. They have demonstrated roles in cancer development and progression and are frequently dysregulated. Here we review the biogenesis and mechanism of action, expression patterns, and detection methods of two types of sncRNAs frequently described in cancer: miRNAs and piRNAs. Both miRNAs and piRNAs have been observed to play both oncogenic and tumor-suppressive roles, with miRNAs acting to directly regulate the mRNA of key cancer-associated genes, while piRNAs play crucial roles in maintaining the integrity of the epigenetic landscape. Elucidating these important functions of sncRNAs in normal and cancer biology relies on numerous in silico workflows and tools to profile sncRNA expression. Thus, we also discuss the key detection methods for cancerrelevant sncRNAs, including the discovery of genes that have yet to be described.

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Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing

Cited by 29 publications

References 36 publications

Analysis of deep sequencing Exosome-microRNA expression profile from Chicken Type Ⅱ Pneumocytes derived reveals potential role of gga-miRNA-451 in inflammation

Analysis of deep sequencing Exosome-microRNA expression profile from Chicken Type Ⅱ Pneumocytes derived reveals potential role of gga-miRNA-451 in inflammation

Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition

Small Noncoding RNA Expression in Cancer

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