Previous Issue
Volume 10, December
 
 

Non-Coding RNA, Volume 11, Issue 1 (February 2025) – 17 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
14 pages, 8695 KiB  
Article
Combinatorial Analysis of miRNAs and tRNA Fragments as Potential Biomarkers for Cancer Patients in Liquid Biopsies
by Ilias Glogovitis, Silvia D’Ambrosi, Mafalda Antunes-Ferreira, Monica Chiogna, Galina Yahubyan, Vesselin Baev, Thomas Wurdinger and Danijela Koppers-Lalic
Non-Coding RNA 2025, 11(1), 17; https://doi.org/10.3390/ncrna11010017 - 14 Feb 2025
Abstract
Background: Liquid biopsy has gained significant attention as a non-invasive method for cancer detection and monitoring. IsomiRs and tRNA-derived fragments (tRFs) are small non-coding RNAs that arise from non-canonical microRNA (miRNAs) processing and the cleavage of tRNAs, respectively. These small non-coding RNAs have [...] Read more.
Background: Liquid biopsy has gained significant attention as a non-invasive method for cancer detection and monitoring. IsomiRs and tRNA-derived fragments (tRFs) are small non-coding RNAs that arise from non-canonical microRNA (miRNAs) processing and the cleavage of tRNAs, respectively. These small non-coding RNAs have emerged as pro-mising cancer biomarkers, and their distinct expression patterns highlight the need for further exploration of their roles in cancer research. Methods: In this study, we investigated the differential expression profiles of miRNAs, isomiRs, and tRFs in plasma extracellular vesicles (EVs) from colorectal and prostate cancer patients compared to healthy controls. Subsequently, a combinatorial analysis using the CombiROC package was performed to identify a panel of biomarkers with optimal diagnostic accuracy. Results: Our results demonstrate that a combination of miRNAs, isomiRs, and tRFs can effectively di- stinguish cancer patients from healthy controls, achieving accuracy and an area under the curve (AUC) of approximately 80%. Conclusions: These findings highlight the potential of a combinatorial approach to small RNA analysis in liquid biopsies for improved cancer diagnosis and management. Full article
(This article belongs to the Special Issue Extracellular Vesicles and ncRNA)
Show Figures

Figure 1

25 pages, 881 KiB  
Review
Psoriasis Treatments: Emerging Roles and Future Prospects of MicroRNAs
by Li Tian Keane Teo, Nerissa Juantuah-Kusi, Gowtham Subramanian and Prabha Sampath
Non-Coding RNA 2025, 11(1), 16; https://doi.org/10.3390/ncrna11010016 - 13 Feb 2025
Abstract
Psoriasis, a widespread and chronic inflammatory skin disorder, is marked by its persistence and the lack of a definitive cure. The pathogenesis of psoriasis is increasingly understood, with ongoing research highlighting the intricate interplay of genetic, immunological, and environmental factors. Recent advancements have [...] Read more.
Psoriasis, a widespread and chronic inflammatory skin disorder, is marked by its persistence and the lack of a definitive cure. The pathogenesis of psoriasis is increasingly understood, with ongoing research highlighting the intricate interplay of genetic, immunological, and environmental factors. Recent advancements have illuminated the pivotal role of microRNAs in orchestrating complex processes in psoriasis and other hyperproliferative skin diseases. This narrative review highlights the emerging significance of miRNAs as key regulators in psoriasis pathogenesis and examines their potential as therapeutic targets. We discuss current treatment approaches and the promising future of miRNAs as next-generation therapeutic agents for this condition. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

10 pages, 362 KiB  
Review
The Small Non-Coding RNA Profile of Human and Mouse Sperm
by Yoon Sing Yap, Pasquale Patrizio, Luisa Cimmino, Konstantinos Sdrimas and Aristeidis G. Telonis
Non-Coding RNA 2025, 11(1), 15; https://doi.org/10.3390/ncrna11010015 - 9 Feb 2025
Abstract
Small non-coding RNAs constitute a dynamic epigenetic layer in mature spermatozoa that can exert transgenerational regulatory functions. Here, we review recent advances in the field of small RNAs in spermatozoa, how their profiles change in response to lifestyle or environmental factors, and their [...] Read more.
Small non-coding RNAs constitute a dynamic epigenetic layer in mature spermatozoa that can exert transgenerational regulatory functions. Here, we review recent advances in the field of small RNAs in spermatozoa, how their profiles change in response to lifestyle or environmental factors, and their impact on offsprings’ physiology. The profile of these RNAs changes dramatically during spermatozoa maturation. The majority of intracellular small RNAs during early spermatogenesis are miRNAs and piRNAs, but, in mature spermatozoa, tRNA- and rRNA-derived fragments (tRFs and rRFs, respectively) are the predominant forms, primarily delivered from the epididymis via extracellular vesicles. Diet, exercise, and environmental exposures have a direct effect on small RNA levels in spermatozoa, and this differential abundance can reprogram the development of the embryo. Offsprings of fathers with different lifestyles can have different phenotypes, including altered metabolism or behavior. Therefore, small RNAs in spermatozoa are emerging as an important epigenetic layer in development and transgenerational inheritance. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

17 pages, 1920 KiB  
Review
The Role of microRNA in the Regulation of Differentiation and the Functionality of Osteoblasts, Osteoclasts, and Their Precursors in Osteoporosis
by Bulat I. Yalaev, Elena I. Kaletnik, Yulia S. Karpova, Zhanna E. Belaya, Ildar R. Minniakhmetov, Natalia G. Mokrysheva and Rita I. Khusainova
Non-Coding RNA 2025, 11(1), 14; https://doi.org/10.3390/ncrna11010014 - 8 Feb 2025
Abstract
Osteoporosis is a complex disease that is affected by a variety of factors, including genetic and epigenetic influences. While DNA markers for osteoporosis have been identified, they do not fully explain the hereditary basis of the disease. Epigenetic factors, such as small microRNAs [...] Read more.
Osteoporosis is a complex disease that is affected by a variety of factors, including genetic and epigenetic influences. While DNA markers for osteoporosis have been identified, they do not fully explain the hereditary basis of the disease. Epigenetic factors, such as small microRNAs (miRNAs), may provide a missing link in understanding the molecular mechanisms underlying osteoporosis. miRNAs are a class of non-coding RNAs that play a role in the epigenetic regulation of gene expression. They are known to be involved in various biological processes, including bone formation and remodelling. Differential expression of miRNAs has been linked to the pathological decrease in bone mineral density associated with osteoporosis. It has been shown that an abnormal miRNA expression pattern leads to a decrease in osteoblast activity and an increase in osteoclast activity. Further research into the role of miRNAs in osteoporosis may help to better understand this disease and identify potential therapeutic targets for treatment. Based on these assumptions, the study of miRNA expression patterns in osteoblasts, osteoclasts, and their precursors under normal and osteoporotic conditions is a rapidly growing field of scientific research. Although the results of this research are still incomplete and sometimes contradictory, they require additional scientific analysis to better understand the complex mechanisms involved. The purpose of this paper is to review the current research on miRNAs specifically expressed in osteoblasts and osteoclasts under both normal and pathological conditions. We will also discuss the potential applications of these miRNAs as biomarkers for osteoporosis diagnosis and as targets for osteoporosis treatment. Full article
Show Figures

Figure 1

11 pages, 1588 KiB  
Article
Circulating MicroRNAs in Patients with Vulvar Squamous Cell Carcinoma and Its Precursors
by Julia Rymuza, Angelika Długosz, Kamil Zalewski, Artur Kowalik, Mateusz Bujko and Magdalena Kowalewska
Non-Coding RNA 2025, 11(1), 13; https://doi.org/10.3390/ncrna11010013 - 7 Feb 2025
Abstract
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of [...] Read more.
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of high-risk human papillomavirus (hrHPV). This study aimed to quantify the circulating microRNAs (miRNAs) in the plasma of patients with premalignant conditions (dVIN and HSILs) and VSCC using TaqMan Low-Density Arrays. Methods: Plasma samples were collected from 40 patients, including those treated for HSILs, dVIN, and VSCC. Quantitative real-time PCR (qRT-PCR) identified the circulating miRNAs differentially expressed in the plasma of VSCC patients compared to patients with precancerous lesions. Results: A total of 31 differentially expressed miRNAs (DEMs) were found to be significantly upregulated in plasma from VSCC patients compared to precancerous cases. None of the analyzed miRNAs were able to distinguish VSCC cases based on hrHPV tumor status. Conclusions: This study provides strong evidence that a distinct set of miRNAs can differentiate between plasma samples from VSCC patients and those with precancerous lesions. Thus, these DEMs have potential diagnostic and prognostic value. “Predisposing” DEMs could be developed as biomarkers to aid in the assessment of vulvar lesions, helping to exclude or confirm progression toward cancer. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
Show Figures

Figure 1

13 pages, 2041 KiB  
Article
Cleft Palate Induced by Mycophenolate Mofetil Is Associated with miR-4680-3p and let-7c-5p in Human Palate Cells
by Hiroki Yoshioka, Hanane Horita, Yosuke Tsukiboshi, Hisaka Kurita, Aya Ogata and Kenichi Ogata
Non-Coding RNA 2025, 11(1), 12; https://doi.org/10.3390/ncrna11010012 - 6 Feb 2025
Abstract
Background/Objectives: Cleft palate is a birth defect associated with environmental and genetic factors. Disturbance of microRNAs (miRNAs) and exposure to medicinal agents during pregnancy can cause cleft palate. Although an association between medicine-induced cleft palate and miRNAs has been suggested, it remains [...] Read more.
Background/Objectives: Cleft palate is a birth defect associated with environmental and genetic factors. Disturbance of microRNAs (miRNAs) and exposure to medicinal agents during pregnancy can cause cleft palate. Although an association between medicine-induced cleft palate and miRNAs has been suggested, it remains to be fully elucidated. This study aimed to clarify the molecular mechanism underlying mycophenolate mofetil (MPM)-induced inhibition of cell proliferation and miRNA expression in human embryonic palatal mesenchymal (HEPM) cells. Methods: Cell viability, apoptosis, and cell cycle-related markers were evaluated 48 h after MPM treatment. In addition, miRNA levels and expression of their downstream genes were measured, and a rescue experiment was performed using miR-4680-3p and/or let-7c-5p inhibitors. Results: MPM dose-dependently reduced HEPM cell viability. Additionally, MPM treatment suppressed cyclin-D1, cyclin E1, cyclin-dependent kinase (CDK)-2, and CDK6 expression in HEPM cells. Furthermore, MPM upregulated miR-4680-3p and let-7c-5p expression and downregulated the downstream genes of each miRNA. Moreover, miR-4680-3p and/or let-7c-5p inhibitors alleviated MPM-induced inhibition of cell proliferation. Conclusions: These results suggest that MPM-induced cleft palate is associated with miR-4680-3p and let-7c-5p expression in HEPM cells. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

22 pages, 5404 KiB  
Article
miRNA Library Preparation Optimisation for Low-Concentration and Low-Volume Paediatric Plasma Samples
by Oenone Rodgers, Chris Watson and Thomas Waterfield
Non-Coding RNA 2025, 11(1), 11; https://doi.org/10.3390/ncrna11010011 - 5 Feb 2025
Abstract
Background: Analysing circulating miRNAs in paediatric plasma is challenging due to typically low sample volumes. The QIAseq miRNA UDI Library Kit (Qiagen, Hilden, Germany) was selected as it has a proven track record with a specific protocol for plasma and serum. The protocol, [...] Read more.
Background: Analysing circulating miRNAs in paediatric plasma is challenging due to typically low sample volumes. The QIAseq miRNA UDI Library Kit (Qiagen, Hilden, Germany) was selected as it has a proven track record with a specific protocol for plasma and serum. The protocol, however, required optimisation for use with low-volume paediatric plasma samples before generating acceptable yields in our cohort. Methods: The miRNeasy Serum/Plasma kit (Qiagen) and the MagMAX miRVana Total Isolation kit (ThermoFisher Scientific, Waltham, MA, USA) were assessed following the manufacturer’s instructions with 100 µL and 200 µL of paediatric plasma. Libraries were prepared using the QIAseq miRNA UDI Library Kit (Qiagen). Optimisations were made for the QIAseq miRNA UDI Library Kit (Qiagen) using total RNA extracted with the miRNeasy Serum/Plasma kit (Qiagen) from 100 µL of plasma. Results: Prior to optimisation, both RNA extraction kits underperformed with the QIAseq miRNA UDI Library kit, producing low miRNA library yields ranging between 0 and 1.42 ng/µL. Plasma input volumes of 100 µL and 200 µL demonstrated no significant differences. Adjusting the QIAseq protocol for low RNA concentrations improved miRNA library yields, an average of 5.6 ng/µL and a maximum of 24.3 ng/µL across 92 samples. The optimised protocol showed no age or gender biases with the QIAseq kit. Conclusions: Failure rates in miRNA library preparations are rarely reported, making it hard to gauge whether the 8.7% failure rate observed here is typical. However, given the challenges of using low-concentration, low-volume paediatric plasma, this represents a significant improvement over previous attempts, supporting further research in the field. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

34 pages, 5942 KiB  
Article
Differential Expression of miRNAs Between Young-Onset and Late-Onset Indian Colorectal Carcinoma Patients
by Sumaiya Moiz, Barsha Saha, Varsha Mondal, Debarati Bishnu, Biswajit Das, Bodhisattva Bose, Soumen Das, Nirmalya Banerjee, Amitava Dutta, Krishti Chatterjee, Srikanta Goswami, Soma Mukhopadhyay and Sudarshana Basu
Non-Coding RNA 2025, 11(1), 10; https://doi.org/10.3390/ncrna11010010 - 2 Feb 2025
Abstract
Reports indicate a worldwide increase in the incidence of Early-Onset Colorectal Carcinoma (EOCRC) (<50 years old). In an effort to understand the different modes of pathogenesis in early-onset CRC, colorectal tumors from EOCRC (<50 years old) and Late-Onset patients (LOCRC; >50 years old) [...] Read more.
Reports indicate a worldwide increase in the incidence of Early-Onset Colorectal Carcinoma (EOCRC) (<50 years old). In an effort to understand the different modes of pathogenesis in early-onset CRC, colorectal tumors from EOCRC (<50 years old) and Late-Onset patients (LOCRC; >50 years old) were screened to eliminate microsatellite instability (MSI), nuclear β-catenin, and APC mutations, as these are known canonical factors in CRC pathogenesis. Small-RNA sequencing followed by comparative analysis revealed differential expression of 23 miRNAs (microRNAs) specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD and TCGA-READ cohorts, followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed metabolic reprogramming, downregulation of anoikis-regulating pathways, and changes in tissue morphogenesis, potentially leading to anchorage-independent growth and progression of epithelial-mesenchymal transition (EMT). Upregulated targets include proteins present in the basal part of intestinal epithelial cells and genes whose expression is known to correlate with invasion and poor prognosis. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

15 pages, 1200 KiB  
Review
Long Intergenic Non-Coding RNAs and BRCA1 in Breast Cancer Pathogenesis: Neighboring Companions or Nemeses?
by Olalekan Olatunde Fadebi, Thabiso Victor Miya, Richard Khanyile, Zodwa Dlamini and Rahaba Marima
Non-Coding RNA 2025, 11(1), 9; https://doi.org/10.3390/ncrna11010009 - 29 Jan 2025
Abstract
Breast cancer is one of the leading causes of mortality among women, primarily due to its complex molecular landscape and heterogeneous nature. The tendency of breast cancer patients to develop metastases poses significant challenges in clinical management. Notably, mutations in the breast cancer [...] Read more.
Breast cancer is one of the leading causes of mortality among women, primarily due to its complex molecular landscape and heterogeneous nature. The tendency of breast cancer patients to develop metastases poses significant challenges in clinical management. Notably, mutations in the breast cancer gene 1 (BRCA1) significantly elevate breast cancer risk. The current research endeavors employ diverse molecular approaches, including RNA, DNA, and protein studies, to explore avenues for the early diagnosis and treatment of breast cancer. Recent attention has shifted towards long non-coding RNAs (lncRNAs) as promising diagnostic, prognostic, and therapeutic targets in the multifaceted progression of breast cancer. Among these, long intergenic non-coding RNAs (lincRNAs), a specific class of lncRNAs, play critical roles in regulating various aspects of tumorigenesis, including cell proliferation, apoptosis, epigenetic modulation, tumor invasion, and metastasis. Their distinctive expression patterns in cellular and tissue contexts underscore their importance in breast cancer development and progression. Harnessing lincRNAs’ sensitivity and precision as diagnostic, therapeutic, and prognostic markers holds significant promise for the clinical management of breast cancer. However, the potential of lincRNAs remains relatively underexplored, particularly in the context of BRCA1-mutated breast cancer and other clinicopathological parameters such as receptor status and patient survival. Consequently, there is an urgent need for comprehensive investigations into novel diagnostic and prognostic breast cancer biomarkers. This review examines the roles of lincRNAs associated with BRCA1 in the landscape of breast cancer, highlighting the potential avenues for future research and clinical applications. Full article
Show Figures

Figure 1

21 pages, 2376 KiB  
Article
Anti-HIV-1 Effect of the Fluoroquinolone Enoxacin and Modulation of Pro-Viral hsa-miR-132 Processing in CEM-SS Cells
by Verena Schlösser, Helen Louise Lightfoot, Christine Leemann, Aathma Merin Bejoy, Shashank Tiwari, Jeffrey L. Schloßhauer, Valentina Vongrad, Andreas Brunschweiger, Jonathan Hall, Karin J. Metzner and Jochen Imig
Non-Coding RNA 2025, 11(1), 8; https://doi.org/10.3390/ncrna11010008 - 20 Jan 2025
Viewed by 314
Abstract
Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. [...] Read more.
Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between HIV-1 infection and changes of the intrinsic cellular miRNA milieu. This interrelationship may direct potential alterations of the host cells’ environment beneficial for the virus or its suppression of replication. Whether this tightly balanced and controlled battle can be exploited therapeutically remains to be further addressed. In this context, the fluoroquinolone antibiotic Enoxacin has been demonstrated as a potent modulator of miRNA processing. Here, we test the hypothesis that this applies also to selected HIV-1-related miRNAs. Methods: We studied the effect of Enoxacin on HIV-1 replication coupled with miRNA qRT-PCR analysis of HIV-1-related miRNAs in CEM-SS and MT-4 T-cells. The effects of miRNA mimic transfections combined with Enoxacin treatment on HIV-1 replication were assessed. Finally, we employed an in vitro DICER1 cleavage assay to study the effects of Enoxacin on a pro-HIV-1 miRNA hsa-miR-132 processing. Results: We established that Enoxacin, but not the structurally similar compound nalidixic acid, exhibits strong anti-HIV-1 effects in the T-cell line CEM-SS, but not MT-4. We provide experimental data that this effect of Enoxacin is partly attributed to the specific downregulation of mature hsa-miR-132-3p, but not other tested pro- or anti-HIV-1 miRNAs, which is likely due to affecting DICER1 processing. Conclusions: Our findings show an anti-retroviral activity of Enoxacin at least in part by downregulation of hsa-miR-132-3p, which may be relevant for future antiviral therapeutic applications by modulation of the RNA interference pathway. Full article
(This article belongs to the Section Small Non-Coding RNA)
Show Figures

Figure 1

12 pages, 2348 KiB  
Review
The Role of Long Non-Coding RNA in the Pathogenesis of Psoriasis
by Kajetan Kiełbowski, Anna Jędrasiak, Estera Bakinowska and Andrzej Pawlik
Non-Coding RNA 2025, 11(1), 7; https://doi.org/10.3390/ncrna11010007 - 17 Jan 2025
Viewed by 458
Abstract
Psoriasis is a chronic immune-mediated disease with complex pathogenesis. The altered proliferation and differentiation of keratinocytes, together with the activity of dendritic cells and T cells, are crucial drivers of psoriasis progression. Long non-coding RNAs (lncRNAs) are composed of over 200 nucleotides and [...] Read more.
Psoriasis is a chronic immune-mediated disease with complex pathogenesis. The altered proliferation and differentiation of keratinocytes, together with the activity of dendritic cells and T cells, are crucial drivers of psoriasis progression. Long non-coding RNAs (lncRNAs) are composed of over 200 nucleotides and exert a large variety of functions, including the regulation of gene expression. Under pathological conditions, the expression of lncRNAs is frequently dysregulated. Recent studies demonstrated that lncRNAs significantly affect major cellular processes, and their aberrant expression is likely involved in the pathogenesis of various disorders. In this review, we will discuss the role of lncRNAs in the pathophysiology of psoriasis. We will summarize recent studies that investigated the relationships between lncRNAs and keratinocyte proliferation and pro-inflammatory responses. Full article
Show Figures

Figure 1

13 pages, 3151 KiB  
Article
In Silico Prediction of Maize microRNA as a Xanthine Oxidase Inhibitor: A New Approach to Treating Hyperuricemia Patients
by Manas Joshi and Mohd Mabood Khan
Non-Coding RNA 2025, 11(1), 6; https://doi.org/10.3390/ncrna11010006 - 15 Jan 2025
Viewed by 723
Abstract
Introduction: Hyperuricemia is characterized by increased uric acid (UA) in the body. The ability to block xanthine oxidase (XO) is a useful way to check how different bioactive molecules affect hyperuricemia. Previous reports showed the significant effect of corn against hyperuricemia disorder with [...] Read more.
Introduction: Hyperuricemia is characterized by increased uric acid (UA) in the body. The ability to block xanthine oxidase (XO) is a useful way to check how different bioactive molecules affect hyperuricemia. Previous reports showed the significant effect of corn against hyperuricemia disorder with its anti-XO activity. The identification of stable Zea mays miRNA (zma-miR) in humans has opened up a new avenue for speculation about its part in regulating novel human gene targets. Aims: The aim of this study was to investigate the prospects of zma-miRs in XO gene regulation, the possible mechanism, and the interaction analysis of the zma-miR-XO mRNA transcript. Method: Significant features of miRNA-mRNA interaction were revealed using two popular miRNA target prediction software—intaRNA (version 3.3.1) and RNA hybrid (version 2.2.1) Results: Only 12 zma-miR-156 variants, out of the 325 zma-miR’s sequences reported in the miRNA database, efficiently interact with the 3′UTR of the XO gene. Characteristics of miRNA-mRNA interaction were as follows: the positioning of zma-miR-156 variants shows that they all have the same 11-mer binding sites, guanine (G), and uracil (U) loops at the 13th and 14th positions from the 5′ end, and no G: U wobble pairing. These factors are related to the inhibition of functional mRNA expression. Additionally, the zma-miR-156 variants exhibit a single-base variation (SBV), which leads to distinct yet highly effective alterations in their interaction pattern with the XO mRNA transcript and the corresponding free energy values. Conclusion: Therefore, we propose that zma-miR-156 variants may be a promising new bioactive compound against hyperuricemia and related diseases. Full article
Show Figures

Figure 1

15 pages, 1409 KiB  
Article
Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study
by Donatella Coradduzza, Sara Cruciani, Biagio Di Lorenzo, Maria Rosaria De Miglio, Angelo Zinellu, Margherita Maioli, Serenella Medici, Gian Luca Erre and Ciriaco Carru
Non-Coding RNA 2025, 11(1), 5; https://doi.org/10.3390/ncrna11010005 - 14 Jan 2025
Viewed by 417
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship [...] Read more.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship between Humanin levels and ED in RA, as well as the interaction between Humanin and non-coding RNAs such as Long Non-Coding RNA GAS5, microRNA-21 (miR-21), and microRNA-103 (miR-103), remains unclear. Objective: This study aimed to investigate the relationship between circulating Humanin levels, non-coding RNAs (GAS5, miR-21, miR-103), and endothelial dysfunction (ED) in patients with RA. Additionally, we explored the correlation between Humanin expression and specific non-coding RNAs (GAS5, miR-21, and miR-103) to better understand their potential role in vascular health. Methods: Peripheral ED was assessed using flow-mediated pulse amplitude tonometry, with Ln-RHI values <0.51 indicating dysfunction. Humanin levels, GAS5, miR-21, and miR-103 were measured in RA patients. Univariate and multivariate analyses were conducted to determine the relationship between these biomarkers and ED. Kaplan–Meier survival analysis and ROC curve analysis were used to assess the prognostic value of Humanin. Results: Higher Humanin levels were significantly associated with better endothelial function (OR = 0.9774, p = 0.0196). Kaplan–Meier analysis demonstrated that higher Humanin levels correlated with improved survival (p < 0.0001). The non-coding RNAs (GAS5, miR-21, and miR-103) did not show significant associations with ED. Conclusions: Humanin is a potential protective biomarker for endothelial dysfunction and survival in RA patients. Further research is needed to explore the interaction between Humanin and non-coding RNAs in the context of vascular health. Full article
Show Figures

Figure 1

23 pages, 1698 KiB  
Article
Integrative Analysis of Whole-Genome and Transcriptomic Data Reveals Novel Variants in Differentially Expressed Long Noncoding RNAs Associated with Asthenozoospermia
by Maria-Anna Kyrgiafini, Maria Katsigianni, Themistoklis Giannoulis, Theologia Sarafidou, Alexia Chatziparasidou and Zissis Mamuris
Non-Coding RNA 2025, 11(1), 4; https://doi.org/10.3390/ncrna11010004 - 14 Jan 2025
Viewed by 510
Abstract
Background/Objectives: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Emerging evidence suggests that noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play a critical role in the regulation of spermatogenesis and sperm function. Coding regions have a well-characterized [...] Read more.
Background/Objectives: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Emerging evidence suggests that noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play a critical role in the regulation of spermatogenesis and sperm function. Coding regions have a well-characterized role and established predictive value in asthenozoospermia. However, this study was designed to complement previous findings and provide a more holistic understanding of asthenozoospermia, this time focusing on noncoding regions. This study aimed to identify and prioritize variants in differentially expressed (DE) lncRNAs found exclusively in asthenozoospermic men, focusing on their impact on lncRNA structure and lncRNA–miRNA–mRNA interactions. Methods: Whole-genome sequencing (WGS) was performed on samples from asthenozoospermic and normozoospermic men. Additionally, an RNA-seq dataset from normozoospermic and asthenozoospermic individuals was analyzed to identify DE lncRNAs. Bioinformatics analyses were conducted to map unique variants on DE lncRNAs, followed by prioritization based on predicted functional impact. The structural impact of the variants and their effects on lncRNA–miRNA interactions were assessed using computational tools. Gene ontology (GO) and KEGG pathway analyses were employed to investigate the affected biological processes and pathways. Results: We identified 4173 unique variants mapped to 258 DE lncRNAs. After prioritization, 5 unique variants in 5 lncRNAs were found to affect lncRNA structure, while 20 variants in 17 lncRNAs were predicted to disrupt miRNA–lncRNA interactions. Enriched pathways included Wnt signaling, phosphatase binding, and cell proliferation, all previously implicated in reproductive health. Conclusions: This study identifies specific variants in DE lncRNAs that may play a role in asthenozoospermia. Given the limited research utilizing WGS to explore the role of noncoding RNAs in male infertility, our findings provide valuable insights and a foundation for future studies. Full article
(This article belongs to the Special Issue Exploring Non-coding RNAs: Insights into Male Infertility)
Show Figures

Figure 1

21 pages, 1908 KiB  
Review
Perspectives in MicroRNA Therapeutics for Cystic Fibrosis
by Alessia Finotti and Roberto Gambari
Non-Coding RNA 2025, 11(1), 3; https://doi.org/10.3390/ncrna11010003 - 12 Jan 2025
Viewed by 322
Abstract
The discovery of the involvement of microRNAs (miRNAs) in cystic fibrosis (CF) has generated increasing interest in the past years, due to their possible employment as a novel class of drugs to be studied in pre-clinical settings of therapeutic protocols for cystic fibrosis. [...] Read more.
The discovery of the involvement of microRNAs (miRNAs) in cystic fibrosis (CF) has generated increasing interest in the past years, due to their possible employment as a novel class of drugs to be studied in pre-clinical settings of therapeutic protocols for cystic fibrosis. In this narrative review article, consider and comparatively evaluate published laboratory information of possible interest for the development of miRNA-based therapeutic protocols for cystic fibrosis. We consider miRNAs involved in the upregulation of CFTR, miRNAs involved in the inhibition of inflammation and, finally, miRNAs exhibiting antibacterial activity. We suggest that antago-miRNAs and ago-miRNAs (miRNA mimics) can be proposed for possible validation of therapeutic protocols in pre-clinical settings. Full article
Show Figures

Figure 1

24 pages, 5992 KiB  
Article
LncRNA 3222401L13Rik Is Upregulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3
by Sophie Schröder, M. Sadman Sakib, Dennis M. Krüger, Tonatiuh Pena, Susanne Burkhardt, Anna-Lena Schütz, Farahnaz Sananbenesi and André Fischer
Non-Coding RNA 2025, 11(1), 2; https://doi.org/10.3390/ncrna11010002 - 9 Jan 2025
Viewed by 647
Abstract
Aging leads to cognitive decline and increased risk of neurodegenerative diseases. While molecular changes in central nervous system (CNS) cells contribute to this decline, the mechanisms are not fully understood. Long non-coding RNAs (lncRNAs) are key regulators of cellular functions. Background/Objectives: The roles [...] Read more.
Aging leads to cognitive decline and increased risk of neurodegenerative diseases. While molecular changes in central nervous system (CNS) cells contribute to this decline, the mechanisms are not fully understood. Long non-coding RNAs (lncRNAs) are key regulators of cellular functions. Background/Objectives: The roles of lncRNAs in aging, especially in glial cells, are not well characterized. Methods: We investigated lncRNA expression in non-neuronal cells from aged mice and identified 3222401L13Rik, a previously unstudied lncRNA, as upregulated in astrocytes during aging. Results: Knockdown of 3222401L13Rik in primary astrocytes revealed its critical role in regulating genes for neuronal support and synapse organization, a function conserved in human iPSC-derived astrocytes. A 3222401L13Rik interacts with the transcription factor Neuronal PAS Domain Protein 3 (Npas3), and overexpression of Npas3 rescues deficits in astrocytes lacking 3222401L13Rik. Conclusions: These data suggest that 3222401L13Rik upregulation may help delay age-related cognitive decline. Full article
(This article belongs to the Section Clinical Applications of Non-Coding RNA)
Show Figures

Figure 1

26 pages, 2100 KiB  
Review
RNA Metabolism and the Role of Small RNAs in Regulating Multiple Aspects of RNA Metabolism
by Pranav Dawar, Indra Adhikari, Swarupa Nanda Mandal and Bhumika Jayee
Non-Coding RNA 2025, 11(1), 1; https://doi.org/10.3390/ncrna11010001 - 24 Dec 2024
Viewed by 1106
Abstract
RNA metabolism is focused on RNA molecules and encompasses all the crucial processes an RNA molecule may or will undergo throughout its life cycle. It is an essential cellular process that allows all cells to function effectively. The transcriptomic landscape of a cell [...] Read more.
RNA metabolism is focused on RNA molecules and encompasses all the crucial processes an RNA molecule may or will undergo throughout its life cycle. It is an essential cellular process that allows all cells to function effectively. The transcriptomic landscape of a cell is shaped by the processes such as RNA biosynthesis, maturation (RNA processing, folding, and modification), intra- and inter-cellular transport, transcriptional and post-transcriptional regulation, modification, catabolic decay, and retrograde signaling, all of which are interconnected and are essential for cellular RNA homeostasis. In eukaryotes, sRNAs, typically 20–31 nucleotides in length, are a class of ncRNAs found to function as nodes in various gene regulatory networks. sRNAs are known to play significant roles in regulating RNA population at the transcriptional, post-transcriptional, and translational levels. Along with sRNAs, such as miRNAs, siRNAs, and piRNAs, new categories of ncRNAs, i.e., lncRNAs and circRNAs, also contribute to RNA metabolism regulation in eukaryotes. In plants, various genetic screens have demonstrated that sRNA biogenesis mutants, as well as RNA metabolism pathway mutants, exhibit similar growth and development defects, misregulated primary and secondary metabolism, as well as impaired stress response. In addition, sRNAs are both the “products” and the “regulators” in broad RNA metabolism networks; gene regulatory networks involving sRNAs form autoregulatory loops that affect the expression of both sRNA and the respective target. This review examines the interconnected aspects of RNA metabolism with sRNA regulatory pathways in plants. It also explores the potential conservation of these pathways across different kingdoms, particularly in plants and animals. Additionally, the review highlights how cellular RNA homeostasis directly impacts adaptive responses to environmental changes as well as different developmental aspects in plants. Full article
(This article belongs to the Special Issue Non-Coding RNA and Their Regulatory Roles in Plant)
Show Figures

Figure 1

Previous Issue
Back to TopTop