Non-Coding RNA

34 pages, 5942 KiB

Open AccessArticle

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

Viewed by 486

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

Open AccessReview

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

Viewed by 370

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

Open AccessArticle

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 436

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

Open AccessReview

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 566

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

Open AccessArticle

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 800

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

Open AccessArticle

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 478

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

Open AccessArticle

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 594

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

Open AccessReview

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 376

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

Open AccessArticle

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 715

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

Open AccessReview

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 1208

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

Journal Menu

Journal Browser

Non-Coding RNA, Volume 11, Issue 1 (February 2025) – 10 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI