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ncRNAs in Human Diseases and Therapeutics
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ncRNAs in Human Diseases and Therapeutics

A Special Issue of Non-Coding RNA (ISSN 2311-553X) belonging to the section "Detection and Biomarkers of Non-Coding RNA".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 3252

Editors

Prof. Dr. Sujay Paul

E-Mail Website1 Website2
Guest Editor
Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Queretaro 76130, Mexico
Interests: ncRNAs in human diseases; gene regulation; biomarker; therapy; anticancer phytochemicals; plant microRNA; nanotechnology
Special Issues, Collections and Topics in MDPI journals
Dr. Neil Renwick

E-Mail Website
Guest Editor
Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen’s University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
Interests: rare cancer; microRNA; microRNA genetics; microRNA expression; microRNA targeting; microRNA dysregulation; disease mechanisms; disease models; microRNA diagnostics; microRNA therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Non-coding RNAs (ncRNAs) have emerged as central regulators of gene expression, influencing virtually every aspect of human physiology and disease. Once considered transcriptional noise, ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and other regulatory RNA species, are now recognized as key players in cellular homeostasis, development, and pathological processes. Accumulating evidence has demonstrated that dysregulation of ncRNAs contributes to the onset and progression of a wide range of human diseases, including cancer, cardiovascular disorders, neurological diseases, metabolic syndromes, immune dysfunction, and infectious diseases. Through their ability to fine-tune gene expression networks, ncRNAs act as critical molecular nodes that integrate genetic, epigenetic, and environmental signals. Their disease-specific expression patterns and functional relevance make them attractive candidates for biomarkers, therapeutic targets, and prognostic indicators.

Beyond their diagnostic and mechanistic importance, ncRNAs have opened new avenues for therapeutic intervention. ncRNA-based therapeutics are rapidly advancing, with several strategies showing promising preclinical and clinical outcomes. These include antisense oligonucleotides, small interfering RNAs (siRNAs), microRNA mimics, and antimicroRNA (anti-miR)-based therapeutics designed to inhibit pathogenic miRNAs. Anti-miR approaches, in particular, have gained significant attention due to their ability to selectively silence disease-driving miRNAs, offering precision and versatility in treating complex disorders. Additional approaches targeting lncRNAs and circRNAs further expand the therapeutic landscape, although challenges related to delivery, specificity, stability, and off-target effects remain.

This Special Issue, “ncRNAs in Human Diseases and Therapeutics,” aims to provide a comprehensive platform for original research articles and reviews that explore the functional roles of ncRNAs in disease pathogenesis and their translation into therapeutic strategies. Topics of interest include, but are not limited to, the following:

  • Molecular mechanisms of ncRNA regulation in human diseases;
  • ncRNAs as diagnostic, prognostic, and predictive biomarkers;
  • MicroRNA-based therapeutics, including miRNA mimics and antimicroRNA strategies;
  • Therapeutic targeting of lncRNAs and circRNAs;
  • ncRNA involvement in cancer, cardiovascular, neurological, metabolic, immune, and infectious diseases;
  • Challenges and innovations in ncRNA delivery systems and clinical translation.

We welcome contributions that advance fundamental understanding and translational applications of ncRNAs, with the ultimate goal of fostering innovative therapeutic strategies for human diseases.

Prof. Dr. Sujay Paul
Dr. Neil Renwick
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA 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 1800 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

  • non-coding RNAs
  • disease biomarker
  • ncRNA-based therapeutics
  • gene regulation
  • RNA-based drug delivery

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Published Papers (4 papers)

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Research

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23 pages, 4309 KB  
Article
A Transcriptome-Wide Analysis Nominates DIO3OS and C9orf139 as Survival-Associated Long Non-Coding RNAs in Glioblastoma
by Minseon Kim, Seung-Kyoon Kim and Jaeil Han
Non-Coding RNA 2026, 12(5), 36; https://doi.org/10.3390/ncrna12050036 - 7 Sep 2026
Viewed by 162
Abstract
Background: Long non-coding RNAs (lncRNAs) are widely proposed as determinants of temozolomide response in glioblastoma (GBM), but many nominations rest on analyst-derived survival endpoints, screens unadjusted for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and models evaluated with the same data used to select [...] Read more.
Background: Long non-coding RNAs (lncRNAs) are widely proposed as determinants of temozolomide response in glioblastoma (GBM), but many nominations rest on analyst-derived survival endpoints, screens unadjusted for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and models evaluated with the same data used to select them. We asked which lncRNA–outcome associations remain when endpoint definition, confounder adjustment, and external validation are addressed explicitly. Methods: We analyzed 94 IDH-wildtype, temozolomide-treated primary GBM patients from The Cancer Genome Atlas (TCGA), using the rule-based progression-free interval (PFI) of the TCGA Pan-Cancer Clinical Data Resource and overall survival (OS) as separate endpoints. A joint transcriptome-wide discovery for OS was performed across TCGA and the identically processed CPTAC-3 cohort (n = 282, 209 deaths), the latter unselected for IDH status because IDH annotation is unavailable for CPTAC-3, with adjustment for MGMT promoter methylation status, cellular composition, and expression subtype. Nominated transcripts were tested for external validation in two independent CGGA cohorts, and incremental discrimination was assessed as the optimism-corrected change in C-index (ΔC-index), benchmarked against the gain expected from a transcriptome-wide search alone. Results: No lncRNA was associated with PFI at a transcriptome-wide false-discovery rate (FDR) below 0.05. The joint OS discovery nominated DIO3OS, the only transcript reaching transcriptome-wide significance (hazard ratio 1.38 per standard deviation, 95% confidence interval 1.20–1.58, FDR 0.022), and C9orf139 (FDR 0.065); both were independently significant in each discovery cohort and robust to adjustment for MGMT status, cellular composition, and expression subtype. Both, however, were null with reversed point estimates in the two CGGA cohorts, were unassociated with PFI, and added only modest optimism-corrected discrimination (ΔC-index 0.07–0.11), close to what a transcriptome-wide search alone generates. Replication was thus confined to two cohorts sharing a processing pipeline. Conclusions: We nominate DIO3OS and C9orf139 as candidate survival-associated lncRNAs in GBM, requiring prospective evaluation in cohorts with complete IDH annotation and progression endpoints, and show how endpoint definition, selection optimism, and external validation determine which lncRNA associations survive scrutiny. Full article
(This article belongs to the Special Issue ncRNAs in Human Diseases and Therapeutics)
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11 pages, 1760 KB  
Article
Cerebrospinal Fluid miRNA Profiling as a Potential Liquid Biopsy for Vestibular Schwannomas
by Małgorzata Litwiniuk-Kosmala, Maria Makuszewska, Robert Bartoszewicz, Agnieszka Jasińska-Nowacka, Maciej Ołdak, Bartłomiej Gielniewski, Bartosz Wojtaś and Kazimierz Niemczyk
Non-Coding RNA 2026, 12(5), 35; https://doi.org/10.3390/ncrna12050035 - 1 Sep 2026
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Abstract
Background/Objectives: This study aimed to identify a characteristic miRNA expression profile in the CSF of patients diagnosed with vestibular schwannoma and evaluate its potential for tumor assessment. Methods: In this prospective study, 17 CSF and corresponding tumor samples (seven small tumors—SVS [...] Read more.
Background/Objectives: This study aimed to identify a characteristic miRNA expression profile in the CSF of patients diagnosed with vestibular schwannoma and evaluate its potential for tumor assessment. Methods: In this prospective study, 17 CSF and corresponding tumor samples (seven small tumors—SVS and 10 large tumors—LVS) were collected from patients operated on for VS in a Tertiary Academic Center. The miRNA expression was analyzed using high-throughput RNA sequencing (NovaSeq 6000 Illumina). Data were normalized, and a comparative analysis of miRNA expression rankings was performed between VS patients and a public healthy donor dataset. Functional implications were explored using KEGG pathway enrichment analysis. Results: A total of 1633 miRNAs were identified in all CSF samples derived from VS patients. Comparison with healthy donors revealed a moderate ranking correlation (ρ = 0.39), with significant shifts for specific molecules like hsa-miR-766-3p and hsa-miR-182-5p. Only six miRNAs were found to correlate between CSF and tumor tissue, while 16 exhibited a negative correlation. No statistical correlation was found between tumor size and the CSF miRNA profile. KEGG analysis highlighted enriched pathways, including neurotrophin signaling and focal adhesion. Conclusions: The results of our study support the feasibility of miRNA-based CSF liquid biopsy for VS assessment. However, the results of miRNA expression profiling conducted in tumor tissue cannot be directly transferred into CSF sample analyses. Further studies are warranted to explain this phenomenon and to search for reliable miRNA markers of VS progression in the CSF liquid biopsy specimens. Full article
(This article belongs to the Special Issue ncRNAs in Human Diseases and Therapeutics)
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22 pages, 17102 KB  
Article
Urinary Exosomal microRNAs as a Novel Approach to Study People with Multiple Sclerosis and Severe Gait Disability: A Preliminary Observation
by Silvia Grassilli, Andrea Baroni, Marina Pierantoni, Federica Brugnoli, Nicola Lamberti, Sofia Straudi, Fabio Manfredini and Valeria Bertagnolo
Non-Coding RNA 2026, 12(3), 16; https://doi.org/10.3390/ncrna12030016 - 8 May 2026
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Abstract
Background: MiRNAs within extracellular vesicles can encompass body barriers, reflecting stage, progression, and response to treatments of various diseases, including multiple sclerosis (MS)—a chronic immune-mediated disease of the central nervous system that causes progressive disability, with highly variable clinical courses. In this context, [...] Read more.
Background: MiRNAs within extracellular vesicles can encompass body barriers, reflecting stage, progression, and response to treatments of various diseases, including multiple sclerosis (MS)—a chronic immune-mediated disease of the central nervous system that causes progressive disability, with highly variable clinical courses. In this context, urinary exosomal miRNAs could be an appealing source of biomarkers, thanks to their non-invasive and easily repeatable collection. Methods: In this exploratory investigation, we tried to assess if profiling urinary exosomal miRNAs could reveal subtle differences within an apparently homogeneous MS population. The study involved 24 patients with primary or secondary progressive MS, whose urinary exosomes (UEs) were subjected to evaluation of a panel of 87 miRNAs variously correlated with neuroinflammation, cardiovascular functions, and/or involved in MS. Results: We revealed that the examined miRNAs were heterogeneously expressed across the patients, reflecting, as expected, their gender and/or hormonal status. Two miRNAs discriminated against primary or secondary progressive MS, and a panel of 14 commonly upmodulated miRNAs identified patients with longer disease duration and a greater degree of disability. Conclusions: Even if preliminary, these data represent the first relationship between UEs and MS features in humans and suggest that urine could constitute a non-invasive source of exosomal miRNAs, which could prove useful in complementing conventional monitoring to provide a more personalized management of MS patients. Full article
(This article belongs to the Special Issue ncRNAs in Human Diseases and Therapeutics)
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Review

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29 pages, 8925 KB  
Review
Exosomal lncRNAs in Cerebrovascular Diseases: Biomarkers, Pathological Mechanisms, and Therapeutic Potential
by Haiyu Su, Daiju Tao, Jia Teng, Li Zhang, Ying Shen, Renhua Yang, Jiarui Yang, Rongji Sun, Zhiqiang Shen, Peng Chen and Bo He
Non-Coding RNA 2026, 12(5), 32; https://doi.org/10.3390/ncrna12050032 - 24 Aug 2026
Viewed by 364
Abstract
Background: Cerebrovascular diseases have complex pathogenesis and pose a serious threat to human health; thus, novel diagnostic and therapeutic strategies are needed. Small extracellular vesicles (sEVs), commonly referred to as exosomes, are 30–150 nm lipid-bilayer vesicles that shield long noncoding RNAs (lncRNAs) from [...] Read more.
Background: Cerebrovascular diseases have complex pathogenesis and pose a serious threat to human health; thus, novel diagnostic and therapeutic strategies are needed. Small extracellular vesicles (sEVs), commonly referred to as exosomes, are 30–150 nm lipid-bilayer vesicles that shield long noncoding RNAs (lncRNAs) from degradation. Because exosomal lncRNAs are more stable than free lncRNAs in blood and cerebrospinal fluid and can cross the blood–brain barrier, they are promising as biomarkers and therapeutic vectors. This review summarizes the roles and mechanisms of exosomal lncRNAs in cerebrovascular diseases. Methods: This narrative review is based on the experimental literature and focuses on the biological functions and regulatory mechanisms of exosomal lncRNAs in cerebrovascular disorders. Results: As competing endogenous RNAs (ceRNAs), they sequester microRNAs (miRNAs), thereby derepressing downstream target-gene expression and modulating neuronal injury (oxidative stress, apoptosis, neuroinflammation) through the nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways. They show altered profiles in acute stroke (ischemic/hemorrhagic) correlated with neurological deficits, and are relevant to the early diagnosis of chronic diseases (atherosclerosis, aneurysm) and vascular dementia. Conclusions: Exosomal lncRNAs demonstrate promising translational potential in preclinical studies because they combine exosome delivery capabilities with lncRNA regulatory functions, although clinical validation remains limited. Full article
(This article belongs to the Special Issue ncRNAs in Human Diseases and Therapeutics)
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