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Non-coding RNAs and Human Diseases: Current Status and Future Perspectives—2nd Edition

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

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 6690

Special Issue Editors


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Guest Editor
Histology and Embryology Department, Medical University of Warsaw, 02-097 Warsaw, Poland
Interests: heart failure; angiogenesis; miRNA; metabolic syndrome; endothelial cell; macrophage; exosomes
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Histology and Embryology Department, Medical University of Warsaw, 02-097 Warsaw, Poland
Interests: heart failure; angiogenesis; lymphangiogenesis; metabolic syndrome; endothelial cell; cardiac fibrosis; reproduction biology; electron microscopy
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Methodology, Center for Preclinical Research, Medical University of Warsaw, 1B Banacha Street, 02-097 Warsaw, Poland
Interests: molecular biology; epigenetics leukemia; endometriosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Non-coding RNAs (ncRNAs) are RNA molecules that do not serve as templates for protein synthesis but perform housekeeping or regulatory functions. Regulatory ncRNAs as of late have been gaining interest since there is increasing scientific evidence that shows their involvement in many cellular processes, such as proliferation, apoptosis and differentiation. According to the number of nucleotides, regulatory ncRNAs can be divided into main two groups—microRNAs (miRNA) and long non-coding RNAs (lncRNAs). The function of miRNAs is better recognized: they mostly negatively regulate gene expression via translational inhibition or mRNA decay. lncRNAs actions are more complex and less described. There is growing evidence that miRNAs and lncRNAs can interact to regulate gene expression.

Since they can be released into extracellular space and bloodstream, non-coding regulatory transcripts can serve as diagnostic and prognostic markers. Moreover, regulatory ncRNAs are considered therapeutic targets for the treatment of various human diseases. In order to design the most effective diagnostic tools and treatments, it is crucial to understand complicated interactions between regulatory ncRNAs and their impact on cellular mechanisms. The focus of this Special Issue is to underline the most recent discoveries in the field of ncRNA biology. Up-to-date review articles and experimental papers are welcome.

More published papers can be found in the closed Special Issue of our first edition:  "Non-coding RNAs and Human Diseases: Current Status and Future Perspectives".

Dr. Justyna Niderla-Bielińska
Dr. Ewa Jankowska-Steifer
Prof. Dr. Paweł Włodarski
Guest Editors

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Keywords

  • miRNA
  • human disease
  • lncRNA
  • targeted therapy
  • diagnostic biomarkers
  • cell physiology
  • gene silencing
  • epigenetic regulation
  • cancer exosomes

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Published Papers (3 papers)

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Research

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17 pages, 6700 KiB  
Article
Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD
by Nataly Makarenkov, Uri Yoel, Yulia Haim, Yair Pincu, Nikhil S. Bhandarkar, Aryeh Shalev, Ilan Shelef, Idit F. Liberty, Gal Ben-Arie, David Yardeni, Assaf Rudich, Ohad Etzion and Isana Veksler-Lublinsky
Int. J. Mol. Sci. 2024, 25(2), 890; https://doi.org/10.3390/ijms25020890 - 10 Jan 2024
Cited by 1 | Viewed by 1588
Abstract
Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify [...] Read more.
Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)—a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers. Full article
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18 pages, 911 KiB  
Article
Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes
by Sandra Van der Auwera, Sabine Ameling, Katharina Wittfeld, Stefan Frenzel, Robin Bülow, Matthias Nauck, Henry Völzke, Uwe Völker and Hans J. Grabe
Int. J. Mol. Sci. 2024, 25(2), 887; https://doi.org/10.3390/ijms25020887 - 10 Jan 2024
Cited by 2 | Viewed by 1676
Abstract
White matter lesions (WML) emerge as a consequence of vascular injuries in the brain. While they are commonly observed in aging, associations have been established with neurodegenerative and neurological disorders such as dementia or stroke. Despite substantial research efforts, biological mechanisms are incomplete [...] Read more.
White matter lesions (WML) emerge as a consequence of vascular injuries in the brain. While they are commonly observed in aging, associations have been established with neurodegenerative and neurological disorders such as dementia or stroke. Despite substantial research efforts, biological mechanisms are incomplete and biomarkers indicating WMLs are lacking. Utilizing data from the population-based Study of Health in Pomerania (SHIP), our objective was to identify plasma-circulating micro-RNAs (miRNAs) associated with WMLs, thus providing a foundation for a comprehensive biological model and further research. In linear regression models, direct association and moderating factors were analyzed. In 648 individuals, we identified hsa-miR-425-5p as directly associated with WMLs. In subsequent analyses, hsa-miR-425-5p was found to regulate various genes associated with WMLs with particular emphasis on the SH3PXD2A gene. Furthermore, miR-425-5p was found to be involved in immunological processes. In addition, noteworthy miRNAs associated with WMLs were identified, primarily moderated by the factors of sex or smoking status. All identified miRNAs exhibited a strong over-representation in neurodegenerative and neurological diseases. We introduced hsa-miR-425-5p as a promising candidate in WML research probably involved in immunological processes. Mir-425-5p holds the potential as a biomarker of WMLs, shedding light on potential mechanisms and pathways in vascular dementia. Full article
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Review

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25 pages, 2399 KiB  
Review
Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases
by Jae-Joon Shin, Jeongkwang Park, Hyeung-Seob Shin, Imene Arab, Kyoungho Suk and Won-Ha Lee
Int. J. Mol. Sci. 2024, 25(5), 2670; https://doi.org/10.3390/ijms25052670 - 25 Feb 2024
Cited by 4 | Viewed by 2293
Abstract
Over the past century, molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. [...] Read more.
Over the past century, molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review aims to summarize the function of lncRNAs in regulating NF-κB activity in macrophage activation and inflammation, with a particular emphasis on their relevance to human diseases and their potential as therapeutic targets. The insights gained from studies on macrophage lncRNAs, as discussed in this review, could provide valuable knowledge for the development of treatments for various pathological conditions involving macrophages. Full article
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