Emerging Function and Clinical Significance of Exosomal circRNAs in Cancer

Wang, Man; Yu, Fei; Li, Peifeng; Wang, Kun

doi:10.1016/j.omtn.2020.06.008

Cited by 69 publications

(52 citation statements)

References 202 publications

(246 reference statements)

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“…The expression profile of exosomal circRNA is different from that of producer cells ( Li et al, 2015 ; Dou et al, 2016 ), suggesting that circRNAs are actively incorporated into exosomes. Multiple mechanisms have been implicated in RNA sorting into exosomes, including specific RNA sequences and/or secondary structures associated with RNA binding proteins ( O’Brien et al, 2020 ; Wang M. et al, 2020 ). However, the precise mechanisms through which circRNAs are sorted into exosomes are not yet clear.…”

Section: Circrna Is Enriched and Stable In Exosomesmentioning

confidence: 99%

Emerging Roles of Exosomal Circular RNAs in Cancer

Seimiya

Otsuka

Iwata

et al. 2020

Front. Cell Dev. Biol.

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Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed continuous loop. The expression pattern of circRNA varies among cell types and tissues, and many circRNAs are aberrantly expressed in various cancers. Aberrantly expressed circRNAs have been shown to play crucial roles in carcinogenesis, functioning as microRNA sponges or new templates for protein translation. Recent research has shown that circRNAs are enriched in exosomes. Exosomes are secretory vesicles that mediate intercellular communication through the delivery of cargo, including proteins, lipids, DNA, and RNA. Exosome-mediated crosstalk between cancer cells and the tumor microenvironment promotes the epithelial-mesenchymal transition, angiogenesis, and immune escape, and thus may contribute to cancer invasion and metastasis. In this review, we discuss the biological functions of exosomal circRNAs and their significance in cancer progression. Additionally, we discuss the potential clinical applications of exosomal circRNAs as biomarkers and in cancer therapy.

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Section: Circrna Is Enriched and Stable In Exosomesmentioning

confidence: 99%

Emerging Roles of Exosomal Circular RNAs in Cancer

Seimiya

Otsuka

Iwata

et al. 2020

Front. Cell Dev. Biol.

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“…Long non-coding RNAs (lncRNAs) have attracted increasing attention as cancer biomarkers for early screening, diagnosis, prognosis and analysis of treatment responses ( 3 , 4 ). Circular RNA (circRNA) is a new member of the non-coding cancer genome and exhibits distinct properties and diverse cellular functions ( 5 , 6 ). To facilitate the study of cancer-associated lncRNAs, we previously reported the first and second version of the Lnc2Cancer database (Lnc2Cancer 1.0 and 2.0), which enabled users to search all known experimentally supported lncRNAs associated with various human cancers ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data

Gao

Shang

Guo

et al. 2020

Nucleic Acids Research

219

138

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An updated Lnc2Cancer 3.0 (http://www.bio-bigdata.net/lnc2cancer or http://bio-bigdata.hrbmu.edu.cn/lnc2cancer) database, which includes comprehensive data on experimentally supported long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) associated with human cancers. In addition, web tools for analyzing lncRNA expression by high-throughput RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) are described. Lnc2Cancer 3.0 was updated with several new features, including (i) Increased cancer-associated lncRNA entries over the previous version. The current release includes 9254 lncRNA-cancer associations, with 2659 lncRNAs and 216 cancer subtypes. (ii) Newly adding 1049 experimentally supported circRNA-cancer associations, with 743 circRNAs and 70 cancer subtypes. (iii) Experimentally supported regulatory mechanisms of cancer-related lncRNAs and circRNAs, involving microRNAs, transcription factors (TF), genetic variants, methylation and enhancers were included. (iv) Appending experimentally supported biological functions of cancer-related lncRNAs and circRNAs including cell growth, apoptosis, autophagy, epithelial mesenchymal transformation (EMT), immunity and coding ability. (v) Experimentally supported clinical relevance of cancer-related lncRNAs and circRNAs in metastasis, recurrence, circulation, drug resistance, and prognosis was included. Additionally, two flexible online tools, including RNA-seq and scRNA-seq web tools, were developed to enable fast and customizable analysis and visualization of lncRNAs in cancers. Lnc2Cancer 3.0 is a valuable resource for elucidating the associations between lncRNA, circRNA and cancer.

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“…Exosomes exist in multifarious body fluids, including blood, urine, saliva, bronchoalveolar lavage fluid, follicle fluid, and amniotic fluid. 4 Exosomes are composed of proteins, lipids, glycoconjugates, and nucleic acids. Exosomes contain a number of soluble proteins in the lumen that are found to be associated with the membranes, including integral membrane proteins, lipid-anchored membrane proteins, and peripherally associated membrane proteins.…”

Section: Introductionmentioning

confidence: 99%

<p>Profiling and Integrated Analysis of Differentially Expressed Circular RNAs in Plasma Exosomes as Novel Biomarkers for Advanced-Stage Lung Adenocarcinoma</p>

Lin¹,

Xiong²,

Liu³

et al. 2020

OTT

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Purpose Exosomes contain abundant circRNAs and are determined to be involved in the pathogenesis of lung adenocarcinoma (LUAD). Thus, our study aimed to explore new circRNAs in plasma exosomes that could be involved in such pathogenesis. Patients and Methods High-throughput sequencing was used in identifying the alterations in exosomal circRNA expression. Gene ontology functional analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to determine the significant functions and pathways associated with differentially expressed circRNAs. TargetScan and miRanda were used to predict circRNA-targeted microRNAs and mRNAs. CircRNA expression profiles were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Wound healing and Transwell assays were performed to determine the roles of has_circ_0102537 in LUAD progression. Results We identified six significantly upregulated and 214 significantly downregulated circRNAs. GO and KEGG pathway analysis suggested that the differentially expressed circRNAs are involved in the occurrence and development of LUAD. A circRNA–miRNA–mRNA meshwork was established to predict the potential interactions among these RNAs. The circRNA expression profile was then subjected to qRT-PCR for validation. We identified hsa_circ_0102537 to be downregulated in both LUAD plasma exosomes and tissues. GO, KEGG pathway analysis, circRNA–miRNA–mRNA meshwork, and further experiments suggest that hsa_circ_0102537 could be involved in LUAD progression. Conclusion Our study explored a large number of circRNAs that may be involved in the LUAD pathogenesis, thereby supporting the need for further research on both diagnosis biomarkers and the potential intervention therapeutic targets.

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Emerging Function and Clinical Significance of Exosomal circRNAs in Cancer

Cited by 69 publications

References 202 publications

Emerging Roles of Exosomal Circular RNAs in Cancer

Emerging Roles of Exosomal Circular RNAs in Cancer

Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data

<p>Profiling and Integrated Analysis of Differentially Expressed Circular RNAs in Plasma Exosomes as Novel Biomarkers for Advanced-Stage Lung Adenocarcinoma</p>

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