Exosomal circular RNA: a signature for lung cancer progression

Hussen, Bashdar Mahmud; Abdullah, Snur Rasool; Faraj, Goran Sedeeq Hama; Rasul, Mohammed Fatih; Salihi, Abbas; Ghafouri‐Fard, Soudeh; Taheri, Mohammad; Mokhtari, Majid

doi:10.1186/s12935-022-02793-7

Cited by 18 publications

(11 citation statements)

References 209 publications

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“…Although the functions and molecular mechanisms of circRNAs in cancer remain largely unknown, the role of miRNA sponge of circRNAs and the circRNA‐miRNA‐mRNA axis were one of the most important parts 18,19 . circRNAs have also been found in exosomes and could be transferred between different cells via exosomes to realize their functions 20–22 . The significant roles of exosomal circRNAs have also been explored in various cancers, including breast cancer 23–25 .…”

Section: Discussionmentioning

confidence: 99%

“…18,19 cir-cRNAs have also been found in exosomes and could be transferred between different cells via exosomes to realize their functions. [20][21][22] The significant roles of exosomal circRNAs have also been explored in various cancers, including breast cancer. [23][24][25] However, most research has focused on the functions of one exosomal circRNA and has ignored the complex ceRNA networks.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive analysis of the exosomal circRNA‐miRNA‐mRNA network in breast cancer

Mao

Cheng

Huang

et al. 2023

The Journal of Gene Medicine

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Background: Exosomal circular RNAs (circRNAs) played critical roles in tumor development and progression and might be novel biomarkers in the diagnosis and treatment of various cancers. However, the biological functions and clinical implications of exosomal circRNAs in breast cancer are unclear.Methods: Expression profiles of exosomal circRNAs the in exoRBase 2.0 database were used to identify differentially expressed exosomal circRNAs in breast cancer.The LASSO and SVM-RFE algorithms followed by multivariate logistic regression analysis were performed to construct the diagnostic model. The target genes of circRNAs were selected by combing differential expression analysis and CSCD, TargetScan and ENCORI databases. Univariate and multivariate survival analysis were conducted to construct a survival-associated exosomal circRNA-miRNA-mRNA network. GSVA and CIBERSORT algorithms were used to evaluate the cancer hallmarks and immune cells in breast cancer and Spearman correlation analysis was used to investigate their correlations with the circRNA-miRNA-mRNA network.Results: In total, 347 upregulated and three downregulated exosomal circRNAs were identified in breast cancer patients. The diagnostic model based on 14 exosomal circRNAs showed a high area under the curve (AUC) value in both the training (AUC = 0.98) and validation (AUC = 0.94) dataset. In total, 70 miRNAs and 1147 mRNAs were selected as the downstream targets of circRNAs and were revealed to participate in tumor-associated pathways, including the PI3K-AKT, MAPK, RAS and RAP1 pathways, as well as calcium signaling pathways, in addition to transcriptional misregulations. The constructed survival-associated exosomal circRNA-miRNA-mRNA network contained nine exosomal circRNAs, 12 miRNAs and 10 mRNAs, and showed complicated correlations and interactions within networks. Cancer hallmark pathways, including the TGF-β, KRAS and MYC signaling pathways, tumor angiogenesis, epithelial-mesenchymal transition, DNA repair and G2M checkpoint, as well as immune cells, including CD4 + and CD8 + T cells, dendritic cells, mast cells, macrophage cells, memory B cells and natural killer cells, were closely correlated with the circRNA-miRNA-mRNA network. Conclusions:The present study is the first to systematically analyze the exosomal circRNAs in breast cancer. We established an exosomal circRNA diagnostic model and constructed a survival-associated exosomal circRNA-miRNA-mRNA network.Our results revealed the complicated functions and potential mechanisms of the

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the exosomal circRNA‐miRNA‐mRNA network in breast cancer

Mao

Cheng

Huang

et al. 2023

The Journal of Gene Medicine

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“…Circular RNAs (CircRNAs) are an emerging field in cancer research, especially in NSCLC, as they were demonstrated to play pivotal roles in carcinogenesis, tumour formation, proliferation, migration, invasion, and sensitivity to therapy [76] . The first evidence of the presence of circRNA in cancer EVs was reported in 2015 when Li et al, using RNA-seq methods, demonstrated the enrichment of circRNAs in tEVs compared to the cell of origin [77] . However, although many efforts have been made in recent years to understand the role of circRNAs in cancer progression, their impact on NSCLC has not been investigated as carefully as that of other types of non-coding RNAs.…”

Section: Circular Rnasmentioning

confidence: 99%

Immunomodulatory role of EV-derived non-coding RNA in lung cancer

Ghidotti¹,

Petraroia²,

Fortunato³

et al. 2023

Extracell Vesicles Circ Nucleic Acids

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Lung cancer is the deadliest cancer worldwide, primarily because of its metastatic spread. Extracellular vesicles (EVs) are small lipid-bilayer particles released by almost all types of cells. EVs play fundamental roles in cell-cell communication and cell-environment interactions by carrying proteins, nucleic acids such as DNA and RNA (mRNAs, lncRNAs, and miRNAs), and other bioactive molecules that are able to influence the behaviour of recipient cells. EVs have been described as key players in the modulation of tumour progression and the anticancer immune response. In this review, we highlight current knowledge on the role of non-coding RNAs in the modulation of the immune response, focusing on lung cancer. Since EVs are fundamental cell-to-cell mediators, we discuss the current knowledge on the immunomodulatory properties of tumour-derived EVs and, in particular, their ncRNA cargo during the different phases of lung cancer development and progression.

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“…CircRNAs are a class of circular endogenous non-coding RNAs without a 5’ segment cap and 3’ end poly(A) tail structure, formed by covalent bonding, which are mRNA precursors (pre-mRNAs) produced by reverse splicing (back-splicing) and are widely expressed in eukaryotic cells as circular endogenous molecules. The abundance of circRNAs in exosomes is twice as high as in cells, and studies have shown that circRNAs are involved in key processes in the development of lung cancer ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis

Cao,

Liu,

Liu

et al. 2024

Front. Oncol.

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BackgroundLung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis.MethodsFor this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed.ResultsThe study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86.ConclusionOur study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.

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Exosomal circular RNA: a signature for lung cancer progression

Cited by 18 publications

References 209 publications

Comprehensive analysis of the exosomal circRNA‐miRNA‐mRNA network in breast cancer

Comprehensive analysis of the exosomal circRNA‐miRNA‐mRNA network in breast cancer

Immunomodulatory role of EV-derived non-coding RNA in lung cancer

Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis

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