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Cancers
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Circular RNAs in Cancer
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Circular RNAs in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 25051

Special Issue Editors

Dr. Steven G. Gray

E-Mail Website
Guest Editor
Trinity St James’s Cancer Institute, Trinity College Dublin, St James’s Hospital, Dublin, Ireland
Interests: non-coding RNA; epigenetics; biomarkers; thoracic malignancy
Special Issues, Collections and Topics in MDPI journals
Dr. Ruby Lin

E-Mail Website
Guest Editor
Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, Australia; School of Medical Sciences, University of Sydney, Sydney, Australia
Interests: transcriptomics; microRNA therapeutics; genomic technologies; cardiovascular disease; cancer biology; obesity; type 2 diabetes; phage therapy; clinical trial; immunomodulation

Special Issue Information

Dear Colleagues,

Current analyses of the human transcriptome indicate that a mere 2% of the genome corresponds to protein coding transcripts, yet it is estimated that ~ 70%–90% of the genome is transcribed. In effect, this means that the majority of RNA found in a cell is noncoding. Within these noncoding RNAs (or ncRNAs), a variety of subtypes have been identified. One of these ncRNAs called circular RNAs, originally identified as early as 1991, was often dismissed as an artifact of splicing but has now been identified as playing a critical role in many processes, including cancer.

Aberrant expression of circRNAs is common in cancer, where the majority of these circRNAs can affect the regulation of critical tumor suppressors through competitive endogenous RNA (ceRNA) mediated effects, often by acting as “molecular sponges” to limit miRNA availability and affect growth. A common altered pathway affected by circRNAs is epithelial–mesenchymal transition (EMT), a key element in carcinogenesis.

circRNAs were originally considered to be noncoding RNAs, but recent studies have shown that a subset of these may in fact encode peptides, which can affect the stability of critical proteins, resulting in altered cellular proliferation, migration, and invasion.

The purpose of this Special Issue is to bring together a series of articles (both reviews and original research) related to circular RNAs with respect to our knowledge of their roles in cancer carcinogenesis, cancer pathology, and cancer etiology.

Dr. Steven G. Gray
Dr. Ruby Lin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer
  • ncRNA
  • circRNA
  • ceRNA
  • Networks
  • Peptides
  • Pathogenesis
  • Etiology

Published Papers (7 papers)

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Research

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24 pages, 3625 KiB  
Article
Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy
by Hung Ho-Xuan, Gerhard Lehmann, Petar Glazar, Foivos Gypas, Norbert Eichner, Kevin Heizler, Hans J. Schlitt, Mihaela Zavolan, Nikolaus Rajewsky, Gunter Meister and Christina Hackl
Cancers 2021, 13(1), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13010049 - 26 Dec 2020
Cited by 6 | Viewed by 3942
Abstract
Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such [...] Read more.
Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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11 pages, 2636 KiB  
Article
circ2GO: A Database Linking Circular RNAs to Gene Function
by Yanhong Lyu, Maiwen Caudron-Herger and Sven Diederichs
Cancers 2020, 12(10), 2975; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12102975 - 14 Oct 2020
Cited by 10 | Viewed by 2672
Abstract
Circular RNAs (circRNAs) play critical roles in a broad spectrum of physiological and pathological processes, including cancer. Here, we provide a comprehensive database—circ2GO—systematically linking circRNAs to the functions and processes of their linear counterparts. circ2GO contains 148,811 circular human RNAs originating from 12,251 [...] Read more.
Circular RNAs (circRNAs) play critical roles in a broad spectrum of physiological and pathological processes, including cancer. Here, we provide a comprehensive database—circ2GO—systematically linking circRNAs to the functions and processes of their linear counterparts. circ2GO contains 148,811 circular human RNAs originating from 12,251 genes, which we derived from deep transcriptomics after rRNA depletion in a panel of 60 lung cancer and non-transformed cell lines. The broad circRNA expression dataset is mapped to all isoforms of the respective gene. The data are visualized in transcript maps and in heatmaps, to intuitively display a comprehensive portrait for the abundance of circRNAs across transcripts and cell lines. By integrating gene ontology (GO) information for all genes in our dataset, circ2GO builds a connection between circRNAs and their host genes’ biological functions and molecular mechanisms. Additionally, circ2GO offers target predictions for circRNA—microRNA (miRNA) pairs for 25,166 highly abundant circRNAs from 6578 genes and 897 high-confidence human miRNAs. Visualization, user-friendliness, intuitive and advanced forward and reverse search options, batch processing and download options make circ2GO a comprehensive source for circRNA information to build hypotheses on their function, processes, and miRNA targets. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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18 pages, 1889 KiB  
Article
The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?
by Adenilson Leão Pereira, Leandro Magalhães, Rafael Pompeu Pantoja, Gilderlanio Araújo, Ândrea Ribeiro-dos-Santos and Amanda Ferreira Vidal
Cancers 2020, 12(7), 1982; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12071982 - 21 Jul 2020
Cited by 18 | Viewed by 3454
Abstract
Circular RNAs (circRNAs) are a new class of long noncoding RNAs able to perform multiple functions, including sponging microRNAs (miRNAs) and RNA-Binding Proteins (RBPs). They play an important role in gastric carcinogenesis, but its involvement during gastric cancer (GC) development and progression are [...] Read more.
Circular RNAs (circRNAs) are a new class of long noncoding RNAs able to perform multiple functions, including sponging microRNAs (miRNAs) and RNA-Binding Proteins (RBPs). They play an important role in gastric carcinogenesis, but its involvement during gastric cancer (GC) development and progression are not well understood. We gathered miRNA and/or RBPs sponge circRNAs present in GC, and accessed their biological roles through functional enrichment of their target genes or ligand RBPs. We identified 54 sponge circRNAs in GC that are able to sponge 51 miRNAs and 103 RBPs. Then, we evaluated their host gene expression using The Cancer Genome Atlas (TCGA) database and observed that COL1A2 is the most overexpressed gene, which may be due to circHIPK3/miR-29b-c/COL1A2 axis dysregulation. We identified 27 GC-related pathways that may be affected mainly by circPVT1, circHIPK3 and circNF1. Our results indicate that circHIPK3/miR-107/BDNF/LIN28 axis may mediate chemoresistance in GC, and that circPVT1, circHIPK3, circNF1, ciRS-7 and circ_0000096 appear to be involved in gastrointestinal cancer development. Lastly, circHIPK3, circNRIP1 and circSMARCA5 were identified in different ethnic populations and may be ubiquitous modulators of gastric carcinogenesis. Overall, the studied sponge circRNAs are part of a complex RBP-circRNA-miRNA-mRNA interaction network, and are involved in the establishment, chemoresistance and progression of GC. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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Review

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22 pages, 1105 KiB  
Review
The Role of circRNAs in Human Papillomavirus (HPV)-Associated Cancers
by Patrizia Bonelli, Antonella Borrelli, Franca Maria Tuccillo, Franco Maria Buonaguro and Maria Lina Tornesello
Cancers 2021, 13(5), 1173; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13051173 - 09 Mar 2021
Cited by 12 | Viewed by 3010
Abstract
Circular RNAs (circRNAs) are a new class of “non-coding RNAs” that originate from non-sequential back-splicing of exons and/or introns of precursor messenger RNAs (pre-mRNAs). These molecules are generally produced at low levels in a cell-type-specific manner in mammalian tissues, but due to their [...] Read more.
Circular RNAs (circRNAs) are a new class of “non-coding RNAs” that originate from non-sequential back-splicing of exons and/or introns of precursor messenger RNAs (pre-mRNAs). These molecules are generally produced at low levels in a cell-type-specific manner in mammalian tissues, but due to their circular conformation they are unaffected by the cell mRNA decay machinery. circRNAs can sponge multiple microRNAs or RNA-binding proteins and play a crucial role in the regulation of gene expression and protein translation. Many circRNAs have been shown to be aberrantly expressed in several cancer types, and to sustain specific oncogenic processes. Particularly, in virus-associated malignancies such as human papillomavirus (HPV)-associated anogenital carcinoma and oropharyngeal and oral cancers, circRNAs have been shown to be involved in tumorigenesis and cancer progression, as well as in drug resistance, and some are useful diagnostic and prognostic markers. HPV-derived circRNAs, encompassing the HPV E7 oncogene, have been shown to be expressed and to serve as transcript for synthesis of the E7 oncoprotein, thus reinforcing the virus oncogenic activity in HPV-associated cancers. In this review, we summarize research advances in the biogenesis of cell and viral circRNAs, their features and functions in the pathophysiology of HPV-associated tumors, and their importance as diagnostic, prognostic, and therapeutic targets in anogenital and oropharyngeal and oral cancers. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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22 pages, 2176 KiB  
Review
The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers
by Peixin Dong, Daozhi Xu, Ying Xiong, Junming Yue, Kei Ihira, Yosuke Konno and Hidemichi Watari
Cancers 2020, 12(6), 1472; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061472 - 04 Jun 2020
Cited by 32 | Viewed by 4000
Abstract
Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs and certain circRNAs are linked to human tumors. Owing to their circular form, circRNAs are protected from degradation by exonucleases, and therefore, they are more stable than linear RNAs. Many circRNAs have been shown [...] Read more.
Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs and certain circRNAs are linked to human tumors. Owing to their circular form, circRNAs are protected from degradation by exonucleases, and therefore, they are more stable than linear RNAs. Many circRNAs have been shown to sponge microRNAs, interact with RNA-binding proteins, regulate gene transcription, and be translated into proteins. Mounting evidence suggests that circRNAs are dysregulated in cancer tissues and can mediate various signaling pathways, thus affecting tumorigenesis, metastasis, and remodeling of the tumor microenvironment. First, we review the characteristics, biogenesis, and biological functions of circRNAs, and describe various mechanistic models of circRNAs. Then, we provide a systematic overview of the functional roles of circRNAs in gynecological cancers. Finally, we describe the potential future applications of circRNAs as biomarkers for prognostic stratification and as therapeutic targets in gynecological cancers. Although the function of most circRNAs remains elusive, some individual circRNAs have biologically relevant functions in cervical cancer, ovarian cancer, and endometrial cancer. Certain circRNAs have the potential to serve as biomarkers and therapeutic targets in gynecological cancers. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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13 pages, 629 KiB  
Review
Functional and Clinical Impact of CircRNAs in Oral Cancer
by Ion Cristóbal, Cristina Caramés, Jaime Rubio, Marta Sanz-Alvarez, Melani Luque, Juan Madoz-Gúrpide, Federico Rojo and Jesús García-Foncillas
Cancers 2020, 12(4), 1041; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12041041 - 23 Apr 2020
Cited by 14 | Viewed by 2801
Abstract
The increasing number of recently published works regarding the role of circular RNAs (circRNAs) in oral cancer highlights the key contribution of this novel class of endogenous noncoding RNAs as regulators of critical signaling pathways and their clinical value as novel biomarkers. This [...] Read more.
The increasing number of recently published works regarding the role of circular RNAs (circRNAs) in oral cancer highlights the key contribution of this novel class of endogenous noncoding RNAs as regulators of critical signaling pathways and their clinical value as novel biomarkers. This review summarizes and puts into context the existing literature in order to clarify the relevance of circRNAs as novel mediators of oral cancer pathogenesis as well as their potential usefulness as predictors of clinical outcome and response to therapy in this disease. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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13 pages, 1792 KiB  
Review
Circulating miR-21 as a Potential Biomarker for the Diagnosis of Oral Cancer: A Systematic Review with Meta-Analysis
by Mario Dioguardi, Giorgia Apollonia Caloro, Luigi Laino, Mario Alovisi, Diego Sovereto, Vito Crincoli, Riccardo Aiuto, Erminia Coccia, Giuseppe Troiano and Lorenzo Lo Muzio
Cancers 2020, 12(4), 936; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12040936 - 10 Apr 2020
Cited by 46 | Viewed by 4046
Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head–neck region and is characterized by the presence of squamous carcinomatous cells of the multi-layered epithelium lining the oral cavity, larynx, and pharynx. The annual incidence of squamous [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head–neck region and is characterized by the presence of squamous carcinomatous cells of the multi-layered epithelium lining the oral cavity, larynx, and pharynx. The annual incidence of squamous cell carcinoma of the head and neck (HNSCC) comprises approximately 600,000 new cases globally. Currently, the 5-year survival from HNSCC is less than 50%. Surgical, radiotherapy, and chemotherapy treatments strongly compromise patient quality of life. MicroRNAs (miRNAs) are a family of small noncoding endogenous RNAs that function in regulating gene expression by regulating several biological processes, including carcinogenesis. The main upregulated microRNAs associated with oral carcinoma are miR-21, miR-455-5p, miR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181, while the main downregulated miRNAs are miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b. miR-21 represents one of the first oncomirs studied. The present systematic review work was performed based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocol. A search was carried out in the PubMed and Scopus databases with the use of keywords. This search produced 628 records which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 7 included articles. The heterogeneity of the studies according to the odds ratio was high, with a Q value of 26.616 (p < 0.001), and the I2 was 77.457% for specificity. The heterogeneity was high, with a Q value of 25.243 (p < 0.001) and the I2 was 76.231% for sensitivity. The heterogeneity of data showed a Q value of 27.815 (p < 0.001) and the I2 was 78.429%. Therefore, the random-effects model was selected. The diagnostic odds ratio was 7.620 (95% CI 3.613–16.070). The results showed that the sensitivity was 0.771 (95% CI 0.680–0.842) (p < 0.001) while, for specificity, we found 0.663 (95% CI 0.538–0.770) (p < 0.001). The negative likelihood ratio (NLR) was 0.321 (95% CI 0.186–0.554), and the positive likelihood ratio (PLR) was 2.144 (95% CI 1.563–2.943). The summary ROC plot demonstrates that the diagnostic test presents good specificity and sensitivity, and the area under the curve (AUC), as calculated from the graph, was 0.79. Full article
(This article belongs to the Special Issue Circular RNAs in Cancer)
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