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Advances in circRNA Biology
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Advances in circRNA Biology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 17586

Special Issue Editor

Dr. Christos K. Kontos

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece
Interests: colorectal cancer; leukemia; tumor biomarkers; anticancer drugs; apoptosis; BCL2 family; alternative splicing; kallikrein-related peptidases (KLKs); nanopore sequencing; next-generation sequencing (NGS)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Circular RNAs (circRNAs) are a new RNA type, deriving from back-splicing. circRNAs have raised researchers’ interest due to their widespread expression and multifaceted role. More specifically, they can act as microRNA sponges, protein sponges or scaffolds, and encode for peptides. Additionally, they play regulatory roles in several cellular processes, including signaling and alternative splicing, both in physiological and pathological states. In particular, their expression has been associated with several aspects of cell life, for instance proliferation and migration, while several studies highlight their value as cancer biomarkers and therapeutic targets.

This Special Issue focuses on the information of the readers regarding the biogenesis and action mechanisms, targets and clinical utility of circRNAs in human physiological and pathological states, with emphasis on cancer, neurodegenerative, cardiovascular and other diseases. The authors are encouraged to submit their original research studies concerning this topic. Review articles will also be taken into consideration. The Guest Editor is willing to evaluate also manuscripts describing other aspects of circRNA Biology, proposed by the authors.

Dr. Christos K. Kontos
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • microRNA (miRNA)
  • long non-coding RNA (lncRNA)
  • alternative splicing
  • regulation of signaling pathways
  • biomarkers
  • therapeutic targets
  • therapy resistance
  • cancer
  • neurological diseases
  • cardiovascular diseases

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Published Papers (6 papers)

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Research

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17 pages, 11232 KiB  
Article
Whole-Transcriptome Sequencing of Antler Tissue Reveals That circRNA2829 Regulates Chondrocyte Proliferation and Differentiation via the miR-4286-R+1/FOXO4 Axis
by Haibo Yao, Renfeng Jiang, Danyang Chen, Yanjun Li, Mengmeng Song, Zitong Sun, Guohui Long, Lei Wu and Wei Hu
Int. J. Mol. Sci. 2023, 24(8), 7204; https://doi.org/10.3390/ijms24087204 - 13 Apr 2023
Cited by 1 | Viewed by 1748
Abstract
The antler is the unique mammalian organ found to be able to regenerate completely and periodically after loss, and the continuous proliferation and differentiation of mesenchymal cells and chondrocytes together complete the regeneration of the antler. Circular non-coding RNAs (circRNAs) are considered to [...] Read more.
The antler is the unique mammalian organ found to be able to regenerate completely and periodically after loss, and the continuous proliferation and differentiation of mesenchymal cells and chondrocytes together complete the regeneration of the antler. Circular non-coding RNAs (circRNAs) are considered to be important non-coding RNAs that regulate body development and growth. However, there are no reports on circRNAs regulating the antler regeneration process. In this study, full-transcriptome high-throughput sequencing was performed on sika deer antler interstitial and cartilage tissues, and the sequencing results were verified and analyzed. The competing endogenous RNA (ceRNA) network related to antler growth and regeneration was further constructed, and the differentially expressed circRNA2829 was screened out from the network to study its effect on chondrocyte proliferation and differentiation. The results indicated that circRNA2829 promoted cell proliferation and increased the level of intracellular ALP. The analysis of RT-qPCR and Western blot demonstrated that the mRNA and protein expression levels of genes involved in differentiation rose. These data revealed that circRNAs play a crucial regulatory role in deer antler regeneration and development. CircRNA2829 might regulate the antler regeneration process through miR-4286-R+1/FOXO4. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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16 pages, 3171 KiB  
Article
Investigating Circular RNAs Using qRT-PCR; Roundup of Optimization and Processing Steps
by Rares Drula, Cornelia Braicu, Sergiu Chira and Ioana Berindan-Neagoe
Int. J. Mol. Sci. 2023, 24(6), 5721; https://doi.org/10.3390/ijms24065721 - 16 Mar 2023
Cited by 7 | Viewed by 3825
Abstract
Circular RNAs (circRNAs) have gained recent attraction due to their functional versatility and particular structure connected to human diseases. Current investigations are focused on the interplay between their ability to sponge smaller species of RNAs, such as microRNAs (miRNAs), thus influencing their regulatory [...] Read more.
Circular RNAs (circRNAs) have gained recent attraction due to their functional versatility and particular structure connected to human diseases. Current investigations are focused on the interplay between their ability to sponge smaller species of RNAs, such as microRNAs (miRNAs), thus influencing their regulatory activity on gene expression and protein templates. Therefore, their reported implication in various biological processes axis has resulted in an accumulating number of studies. While the testing and annotation methods of novel circular transcripts are still under development, there is still a plethora of transcript candidates suitable for investigation in human disease. The discordance in the literature regarding the approaches used in circRNAs quantification and validation methods, especially regarding qRT-PCR, the current golden standard procedure, leads to high result variability and undermines the replicability of the studies. Therefore, our study will offer several valuable insights into bioinformatic data for experimental design for circRNA investigation and in vitro aspects. Specifically, we will highlight key aspects such as circRNA database annotation divergent primer design and several processing steps, such as RNAse R treatment optimization and circRNA enrichment assessment. Additionally, we will provide insights into the exploration of circRNA-miRNA interactions, a prerequisite for further functional investigations. With this, we aim to contribute to the methodological consensus in a currently expanding field with possible implications for assessing therapeutic targets and biomarker discovery. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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18 pages, 4942 KiB  
Article
BMSC-Derived Exosomal CircHIPK3 Promotes Osteogenic Differentiation of MC3T3-E1 Cells via Mitophagy
by Shaoyang Ma, Sijia Li, Yuchen Zhang, Jiaming Nie, Jiao Cao, Ang Li, Ye Li and Dandan Pei
Int. J. Mol. Sci. 2023, 24(3), 2785; https://doi.org/10.3390/ijms24032785 - 1 Feb 2023
Cited by 16 | Viewed by 3128
Abstract
Exosome-based therapy is emerging as a promising strategy to promote bone regeneration due to exosomal bioactive cargos, among which circular RNA (circRNA) has recently been recognized as the key effector. The role of exosomal circRNA derived from bone marrow mesenchymal stem cells (BMSCs) [...] Read more.
Exosome-based therapy is emerging as a promising strategy to promote bone regeneration due to exosomal bioactive cargos, among which circular RNA (circRNA) has recently been recognized as the key effector. The role of exosomal circRNA derived from bone marrow mesenchymal stem cells (BMSCs) has not been well-defined. The present study aimed to clarify the regulatory function and molecular mechanism of BMSC-derived exosomal circRNA in osteogenesis. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) were isolated and identified. BMSC-Exos’ pro-osteogenic effect on MC3T3-E1 cells was validated by alkaline phosphatase (ALP) activity and Alizarin Red staining. Through bioinformatic analysis and molecular experiments, circHIPK3 was selected and verified as the key circRNA of BMSC-Exos to promote osteoblast differentiation of MC3T3-E1 cells. Mechanistically, circHIPK3 acted as an miR-29a-5p sponge and functioned in mitophagy via targeting miR-29a-5p and PINK1. Additionally, we showed that the mitophagy level of MC3T3-E1 cells were mediated by BMSC-Exos, which promoted the osteogenic differentiation. Collectively, our results revealed an important role for BMSC-derived exosomal circHIPK3 in osteogenesis. These findings provide a potentially effective therapeutic strategy for bone regeneration. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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18 pages, 5279 KiB  
Article
Comprehensive Profiling of ceRNA (circRNA-miRNA-mRNA) Networks in Hypothalamic-Pituitary-Mammary Gland Axis of Dairy Cows under Heat Stress
by Hanfang Zeng, Haibin Xia, Xinling Wang, Yue Wang, Jian Fang, Shujie Li, Yunfei Zhai and Zhaoyu Han
Int. J. Mol. Sci. 2023, 24(1), 888; https://doi.org/10.3390/ijms24010888 - 3 Jan 2023
Cited by 11 | Viewed by 2931
Abstract
Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the [...] Read more.
Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the HPM axis of dairy cows under HS is still unclear. In the present study, we performed RNA sequencing to identify diferentially expressed (DE) circRNAs, DE microRNAs(miRNAs) and DEmRNAs, and performed bioinformatics analysis on those in HPM axis-related tissues of heat-stressed and normal cows. A total of 1680, 1112 and 521 DEcircRNAs, 120, 493 and 108 DEmiRNAs, 274, 6475 and 3134 DEmRNAs were identified in the hypothalamic, pituitary, and mammary gland tissues, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the MAPK signaling pathway is potentially a key pathway. Competitive endogenous RNA (ceRNA) networks related to HS response and lactation regulation were established in three tissues. In conclusion, our results indicate that HS induces differential circRNA expression profiles in HPM axis-related tissues, and the predicted ceRNA network provides a molecular basis for regulating the stress response and lactation regulation in heat-stressed dairy cows. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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Review

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15 pages, 612 KiB  
Review
Virus-Encoded Circular RNAs: Role and Significance in Viral Infections
by Giuseppe Sberna, Fabrizio Maggi and Alessandra Amendola
Int. J. Mol. Sci. 2023, 24(22), 16547; https://doi.org/10.3390/ijms242216547 - 20 Nov 2023
Viewed by 1856
Abstract
Circular RNAs (circRNAs) have been the focus of intense scientific research to understand their biogenesis, mechanisms of action and regulatory functions. CircRNAs are single stranded, covalently closed RNA molecules lacking the 5′-terminal cap and the 3′-terminal polyadenine chain, characteristics that make them very [...] Read more.
Circular RNAs (circRNAs) have been the focus of intense scientific research to understand their biogenesis, mechanisms of action and regulatory functions. CircRNAs are single stranded, covalently closed RNA molecules lacking the 5′-terminal cap and the 3′-terminal polyadenine chain, characteristics that make them very stable and resistant. Synthesised by both cells and viruses, in the past circRNAs were considered to have no precise function. Today, increasing evidence shows that circRNAs are ubiquitous, some of them are tissue- and cell-specific, and critical in multiple regulatory processes (i.e., infections, inflammation, oncogenesis, gene expression). Moreover, circRNAs are emerging as important biomarkers of viral infection and disease progression. In this review, we provided an updated overview of current understanding of virus-encoded and cellular-encoded circRNAs and their involvement in cellular pathways during viral infection. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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23 pages, 6469 KiB  
Review
Emerging Role of Circular RNAs in Hepatocellular Carcinoma Immunotherapy
by Tasneem Abaza, Mostafa K. Abd El-Aziz, Kerolos Ashraf Daniel, Paraskevi Karousi, Maria Papatsirou, Sherif Ashraf Fahmy, Nadia M. Hamdy, Christos K. Kontos and Rana A. Youness
Int. J. Mol. Sci. 2023, 24(22), 16484; https://doi.org/10.3390/ijms242216484 - 18 Nov 2023
Cited by 17 | Viewed by 3269
Abstract
Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged as a new paradigm shift in oncology. ICIs, such as programmed cell death protein 1 (PD-1) [...] Read more.
Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged as a new paradigm shift in oncology. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have provided a new source of hope for patients with advanced HCC. Yet, the eligibility criteria of HCC patients for ICIs are still a missing piece in the puzzle. Circular RNAs (circRNAs) have recently emerged as a new class of non-coding RNAs that play a fundamental role in cancer pathogenesis. Structurally, circRNAs are resistant to exonucleolytic degradation and have a longer half-life than their linear counterparts. Functionally, circRNAs possess the capability to influence various facets of the tumor microenvironment, especially at the HCC tumor–immune synapse. Notably, circRNAs have been observed to control the expression of immune checkpoint molecules within tumor cells, potentially impeding the therapeutic effectiveness of ICIs. Therefore, this renders them potential cancer-immune biomarkers for diagnosis, prognosis, and therapeutic regimen determinants. In this review, the authors shed light on the structure and functional roles of circRNAs and, most importantly, highlight the promising roles of circRNAs in HCC immunomodulation and their potential as promising biomarkers and immunotherapeutic regimen determinants. Full article
(This article belongs to the Special Issue Advances in circRNA Biology)
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