Circulating RNAs in Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 10696

Special Issue Editors


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Guest Editor
Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
Interests: molecular medicine; novel diagnostic approaches; genetic diseases; cancer; next generation sequencing; mutation detection; non-coding RNAs as biomarkers
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Guest Editor
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
Interests: regulation of gene expretion through epigenetics and non-coding RNAs; genetic polymorphysms and mutations; non coding RNAs (miRNAs, lncRNAs, circRNAs) as circulating biomarkers in diseases of neurodegeneration and cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The ENCODE (Encyclopedia of DNA Elements) project revealed that large portions of the human genome are transcriptionally active in many forms of noncoding RNAs (ncRNAs). ncRNAs are two main types: structural and regulatory ncRNAs. Structural ncRNAs or house-keeping ncRNAs include small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), guide RNAs (gRNA), RNaseP RNAs that take part in processing transcriptional products, and transfer RNAs (tRNAs), ribosome RNAs (rRNAs), and transfer messenger RNAs (tmRNAs) that are involved in protein translation. Regulatory ncRNAs are more interesting from an epigenetic point of view due to their role as intracellular regulators of gene expression maintaining proper functioning of critical biological processes, including development, growth, homeostasis and aging, while their dysregulation is implicated in a myriad of diseases. Regulatory ncRNAs include microRNAs (miRNA), long noncoding RNAs (lncRNA), piwi interaction RNAs (piRNAs), and circular RNAs (circRNA).  

Human serum and plasma and other bodily fluids contain various classes of RNA molecules, including regulatory ncRNAs. Several types of regulatory ncRNAs are released into the circulation system mainly through the following mechanisms:

(i) Exosomes and microvesicles;

(ii) Apoptotic bodies; and

(iii) Protein complexes, such as RNA-binding proteins. 

Since ncRNAs are protected in exosomes, microvesicles, apoptotic bodies, and protein complexes, they also exhibit a remarkable stability in diverse body fluids, including those in the circulatory system. Circulating ncRNAs can thus be readily isolated and detected via various molecular methods, allowing them to also serve as potential biomarkers for diseases. There is ample evidence that circulating ncRNAs are involved in cardiovascular diseases, autoimmune diseases, neurodegenerative diseases, and cancer. Moreover, there are also some indications that circulating ncRNAs could serve as biomarkers for medical treatment in (i) selection of therapy, (ii) evaluation of drug efficacy, (iii) optimal dose selection, and (iv) drug side-effect recognition.

In the last decade, the amount of research and the number of publications on associations between circulating RNAs and diseases has grown exponentially.

For this Special Issue, we welcome original papers and reviews on circulating ncRNAs research, which includes, but is not limited to, miRNA, lncRNA, piwi interaction RNAs, and circRNA in all bodily fluids with a potential role as biomarkers in diseases, including cancer and therapy.

Prof. Damjan Glavač
Prof. Metka Ravnik-Glavač
Guest Editors

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Keywords

  • circulating RNAs
  • miRNA,  lncRNA,  piRNA, circRNA
  • blood, saliva, urine, cerebrospinal fluid
  • disease,  cancer

Published Papers (3 papers)

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Research

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10 pages, 816 KiB  
Article
MiR-26a-5p as a Reference to Normalize MicroRNA qRT-PCR Levels in Plasma Exosomes of Pediatric Hematological Malignancies
by Carlotta C. Damanti, Enrico Gaffo, Federica Lovisa, Anna Garbin, Piero Di Battista, Ilaria Gallingani, Anna Tosato, Marta Pillon, Elisa Carraro, Maurizio Mascarin, Caterina Elia, Alessandra Biffi, Stefania Bortoluzzi and Lara Mussolin
Cells 2021, 10(1), 101; https://doi.org/10.3390/cells10010101 - 8 Jan 2021
Cited by 23 | Viewed by 4621
Abstract
Plasma exosomal microRNAs (miRNAs) are considered as valid circulating biomarkers for cancer diagnosis and prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR), the most commonly used technique to assess circulating miRNA levels, requires a normalization step involving uniformly expressed endogenous miRNAs. However, there is [...] Read more.
Plasma exosomal microRNAs (miRNAs) are considered as valid circulating biomarkers for cancer diagnosis and prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR), the most commonly used technique to assess circulating miRNA levels, requires a normalization step involving uniformly expressed endogenous miRNAs. However, there is still no consensus on reference miRNAs for plasma exosomal miRNA abundance normalization. In this study, we identified a panel of miRNAs with stable abundance by analyzing public plasma exosome RNA-seq data and selected miR-486-5p, miR-26a-5p, miR-423-5p and miR191-5p as candidate normalizers. Next, we tested the abundance variation of these miRNAs by qRT-PCR in plasma exosomes of healthy donors and pediatric patients with anaplastic large cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia. MiR-486-5p and miR-26a-5p showed the most stable levels, both between healthy controls and patients and among the malignancies analyzed. In light of previous reports on miRNA stability in different exosome isolation methods, our data indicated that miR-26a-5p is a bona fide reference miRNA for qRT-PCR normalization to evaluate miRNA abundance from circulating plasma exosomes in studies of hematological malignancies. Full article
(This article belongs to the Special Issue Circulating RNAs in Health and Disease)
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14 pages, 481 KiB  
Article
Mutual Interaction of Clinical Factors and Specific microRNAs to Predict Mild Cognitive Impairment in Patients Receiving Hemodialysis
by Jin-Bor Chen, Chiung-Chih Chang, Lung-Chih Li, Wen-Chin Lee, Chia-Ni Lin, Sung-Chou Li, Sin-Hua Moi and Cheng-Hong Yang
Cells 2020, 9(10), 2303; https://doi.org/10.3390/cells9102303 - 15 Oct 2020
Cited by 5 | Viewed by 2108
Abstract
Cognitive impairment (CI) is not uncommon in dialysis patients. Various factors have been implicated. This study aims to examine mutual interaction of various clinical factors for CI in patients receiving hemodialysis. A total of 48 hemodialysis patients in outpatient clinic were recruited from [...] Read more.
Cognitive impairment (CI) is not uncommon in dialysis patients. Various factors have been implicated. This study aims to examine mutual interaction of various clinical factors for CI in patients receiving hemodialysis. A total of 48 hemodialysis patients in outpatient clinic were recruited from 2015 to 2017. Demographics, circulating uremic toxin concentrations, miRNA concentrations, and nerve injury protein concentrations were collected. Clinical dementia rating (CDR) scores were used to stratify the functional scores of the patients. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic test performance for predicting dichotomous results, and cumulative ROC analysis was used to examine the combined contribution of clinical factors. CDR scale 0 included 15 patients (mean age, 59.1 years); CDR > 0.5 included 33 patients (mean age, 64.0 years). On cumulative ROC analysis, the major predictors of mild CI were hemoglobin, age, sex, homocysteine, neuron-specific enolase (NSE), and miR-486. The cumulative area under the curve (AUC) on combining hemoglobin, age, and miR-486 was the highest (0.897, 95% confidence interval 0.806–0.988). Two dichotomized variables reached 81.82% sensitivity and 86.67% specificity, with the likelihood ratio for positive and negative results being 6.14 and 0.21, respectively. In conclusion, hemoglobin, age, and miR-486 display high-degree combined effects on mild CI in patients receiving hemodialysis. Full article
(This article belongs to the Special Issue Circulating RNAs in Health and Disease)
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Review

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13 pages, 1866 KiB  
Review
Circulating Non-Coding RNAs in Head and Neck Cancer: Roles in Diagnosis, Prognosis, and Therapy Monitoring
by Araceli Diez-Fraile, Joke De Ceulaer, Charlotte Derpoorter, Christophe Spaas, Tom De Backer, Philippe Lamoral, Johan Abeloos and Tim Lammens
Cells 2021, 10(1), 48; https://doi.org/10.3390/cells10010048 - 31 Dec 2020
Cited by 16 | Viewed by 3359
Abstract
Head and neck cancer (HNC), the seventh most common form of cancer worldwide, is a group of epithelial malignancies affecting sites in the upper aerodigestive tract. The 5-year overall survival for patients with HNC has stayed around 40–50% for decades, with mortality being [...] Read more.
Head and neck cancer (HNC), the seventh most common form of cancer worldwide, is a group of epithelial malignancies affecting sites in the upper aerodigestive tract. The 5-year overall survival for patients with HNC has stayed around 40–50% for decades, with mortality being attributable mainly to late diagnosis and recurrence. Recently, non-coding RNAs, including tRNA halves, YRNA fragments, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), have been identified in the blood and saliva of patients diagnosed with HNC. These observations have recently fueled the study of their potential use in early detection, diagnosis, and risk assessment. The present review focuses on recent insights and the potential impact that circulating non-coding RNA evaluation may have on clinical decision-making in the management of HNC. Full article
(This article belongs to the Special Issue Circulating RNAs in Health and Disease)
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