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Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0

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

Deadline for manuscript submissions: 28 August 2024 | Viewed by 4823

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Special Issue Editors

Prof. Dr. Kyriacos N. Felekkis

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Guest Editor

Non-Coding RNA Research Laboratory, Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, 2417 Nicosia, Cyprus
Interests: non-coding RNAs; miRNAs; biomarkers; personalized medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Christos Papaneophytou

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Guest Editor

Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
Interests: drug discovery; biomarkers; miRNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Circulating non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and PIWI-interacting RNAs, are a class of stable RNAs that do not encode proteins, which can be detected in body fluids, including blood and urine. Several ncRNAs regulate several cellular functions, such as proliferation, apoptosis, and cell cycle progression. NcRNAs have been reported to contribute at various levels of disease pathogenesis, ranging from causative players to modifying factors. Inevitably, their role in human diseases has become apparent. Additionally, emphasis has been given to the role of these molecules as diagnostic, prognostic, and even therapeutic biomarkers of human diseases. Despite the initial difficulties on that front, due to the high intra- and intervariability, many of these discoveries are currently reaching the clinic. In the era of personalized medicine, elucidating the multifaceted role of ncRNAs in human diseases is considered of utmost importance.

This Special Issue invites submissions of original papers and reviews that cover recent advances in the application of ncRNAs as prognostic and diagnostic biomarkers of human diseases and other related subjects.

Prof. Dr. Kyriacos N. Felekkis
Dr. Christos Papaneophytou
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

miRNA
gene expression regulation
diagnosis
prognosis
therapy
biomarkers

Published Papers (5 papers)

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Research

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14 pages, 1756 KiB

Open AccessArticle

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

by Damian Mikulski, Kacper Kościelny, Izabela Dróżdż, Grzegorz Mirocha, Mateusz Nowicki, Małgorzata Misiewicz, Ewelina Perdas, Piotr Strzałka, Agnieszka Wierzbowska and Wojciech Fendler

Int. J. Mol. Sci. 2024, 25(8), 4355; https://doi.org/10.3390/ijms25084355 - 15 Apr 2024

Viewed by 459

Abstract

Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)—miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p—in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29–3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11–0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63–0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures. Full article

(This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0)

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14 pages, 1529 KiB

Open AccessArticle

The Screening of microRNAs in Chronic Myeloid Leukemia: A Clinical Evaluation

by Denise Kusma Wosniaki, Anelis Maria Marin, Rafaela Noga Oliveira, Gabriela Marino Koerich, Eduardo Cilião Munhoz, João Samuel de Holanda Farias, Miriam Perlingeiro Beltrame, Dalila Luciola Zanette and Mateus Nóbrega Aoki

Int. J. Mol. Sci. 2024, 25(6), 3363; https://doi.org/10.3390/ijms25063363 - 16 Mar 2024

Viewed by 640

Abstract

Chronic myeloid leukemia (CML) is a type of leukemia whose main genetic marker is the reciprocal translocation that leads to the production of the BCR::ABL1 oncoprotein. The expression of some genes may interfere with the progression and development of leukemias. MicroRNAs are small non-coding RNAs that have the potential to alter the expression of some genes and may be correlated with some types of leukemia and could be used as biomarkers in the diagnosis and prognosis of patients. Therefore, this project carried out an analysis of microRNA-type plasma biomarkers in patients with chronic myeloid leukemia at unique points, including follow-up analysis of patients from the Erasto Gaertner Hospital. 35 microRNAs were analyzed in different cohorts. Inside those groups, 70 samples were analyzed at unique points and 11 patients in a follow-up analysis. Statistically different results were found for microRNA-7-5p, which was found to be upregulated in patients with high expression of the BCR::ABL1 transcript when compared to healthy controls. This microRNA also had evidence of behavior related to BCR::ABL1 when analyzed in follow-up, but strong evidence was not found. In this way, this work obtained results that may lead to manifestations of a relationship between miR-7-5p and chronic myeloid leukemia, and evaluations of possible microRNAs that are not related to this pathology. Full article

(This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0)

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20 pages, 1927 KiB

Open AccessArticle

Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans

by Rekha S. Patel, Meredith Krause-Hauch, Kimbra Kenney, Shannon Miles, Risa Nakase-Richardson and Niketa A. Patel

Int. J. Mol. Sci. 2024, 25(3), 1473; https://doi.org/10.3390/ijms25031473 - 25 Jan 2024

Cited by 1 | Viewed by 935

Abstract

More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated with rmTBI years after the incidences. Serum samples were obtained from Long-Term Impact of Military-Relevant Brain-Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC CENC) repository, from participants unexposed to TBI or who had rmTBI. Four lncRNAs were identified as consistently present in all samples, as detected via droplet digital PCR and packaged in exosomes enriched for CNS origin. The results, using qPCR, demonstrated that the lncRNA VLDLR-AS1 levels were significantly lower among individuals with rmTBI compared to those with no lifetime TBI. ROC analysis determined an AUC of 0.74 (95% CI: 0.6124 to 0.8741; p = 0.0012). The optimal cutoff for VLDLR-AS1 was ≤153.8 ng. A secondary analysis of clinical data from LIMBIC CENC was conducted to evaluate the psychological symptom burden, and the results show that lncRNAs VLDLR-AS1 and MALAT1 are correlated with symptoms of depression. In conclusion, lncRNA VLDLR-AS1 may serve as a blood biomarker for identifying chronic rmTBI and depression in patients. Full article

(This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0)

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17 pages, 2116 KiB

Open AccessArticle

Plasma Circular-RNA 0005567 as a Potential Marker of Disease Activity in Rheumatoid Arthritis

by Marek Cieśla, Dorota A. Darmochwal-Kolarz, Konrad Kwaśniak, Anna Pałka and Bogdan Kolarz

Int. J. Mol. Sci. 2024, 25(1), 417; https://doi.org/10.3390/ijms25010417 - 28 Dec 2023

Viewed by 649

Abstract

Circular RNAs (circRNAs) are noncoding molecules and are generated through back splicing, during which the 5′ and 3′ ends are covalently joined. Consequently, the lack of free ends makes them stable and resistant to exonucleases, and they become more suitable biomarkers than other noncoding RNAs. The aim of the study was to find an association between selected circRNAs and disease activity in patients with RA. A total of 71 subjects, 45 patients with RA and 26 healthy controls (HCs), were enrolled. In the RA group, 24 patients had high disease activity (DAS-28-ESR > 5.1) and 21 individuals were in remission (DAS-28-ESR ≤ 2.6). The cell line SW982 was used to evaluate the biological function of circ_0005567. The concentration of circ_0005567 in RA patients was elevated compared to HCs (median, 177.5 [lower–upper quartile, 83.13–234.6] vs. 97.83 [42.03–145.4], p = 0.017). Patients with high disease activity had a higher concentration of circ_0005567 than the control group (185.4 [112.72–249.25] vs. 97.83 [42.03–145.4], p = 0.015). In the cell line model, we found an association between circ_0005567 and miR-194-5p concentration and increased expression of mRNAs that may be related to cell proliferation. The plasma concentration of circ_0005567 may be a new potential biomarker associated with disease activity in patients with RA. Full article

(This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0)

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Review

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30 pages, 1898 KiB

Open AccessReview

The Circulating Biomarkers League: Combining miRNAs with Cell-Free DNAs and Proteins

by Kyriacos Felekkis and Christos Papaneophytou

Int. J. Mol. Sci. 2024, 25(6), 3403; https://doi.org/10.3390/ijms25063403 - 17 Mar 2024

Viewed by 1675

Abstract

The potential of liquid biopsy for the prognosis and diagnosis of diseases is unquestionable. Within the evolving landscape of disease diagnostics and personalized medicine, circulating microRNAs (c-miRNAs) stand out among the biomarkers found in blood circulation and other biological fluids due to their stability, specificity, and non-invasive detection in biofluids. However, the complexity of human diseases and the limitations inherent in single-marker diagnostics highlight the need for a more integrative approach. It has been recently suggested that a multi-analyte approach offers advantages over the single-analyte approach in the prognosis and diagnosis of diseases. In this review, we explore the potential of combining three well-studied classes of biomarkers found in blood circulation and other biofluids—miRNAs, DNAs, and proteins—to enhance the accuracy and efficacy of disease detection and monitoring. Initially, we provide an overview of each biomarker class and discuss their main advantages and disadvantages highlighting the superiority of c-miRNAs over the other classes of biomarkers. Additionally, we discuss the challenges and future directions in integrating these biomarkers into clinical practice, emphasizing the need for standardized protocols and further validation studies. This integrated approach has the potential to revolutionize precision medicine by offering insights into disease mechanisms, facilitating early detection, and guiding personalized therapeutic strategies. The collaborative power of c-miRNAs with other biomarkers represents a promising frontier in the comprehensive understanding and management of complex diseases. Nevertheless, several challenges must be addressed before this approach can be translated into clinical practice. Full article

(This article belongs to the Special Issue Circulating Non-coding RNAs as Diagnostic and Prognostic Markers of Human Diseases 2.0)

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