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Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease

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

Deadline for manuscript submissions: 20 April 2025 | Viewed by 4731

Special Issue Editors

Dr. Marco Ragusa

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics “G. Sichel”, University of Catania, 95123 Catania, Italy
Interests: noncoding RNAs; expression analysis; cell biology; circulating RNAs; exosomes; uveal melanoma; colon cancer; glioblastoma
Special Issues, Collections and Topics in MDPI journals
Dr. Cristina Barbagallo

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics “G. Sichel”, University of Catania, 95123 Catania, Italy
Interests: cancer biology; non-coding RNAs; miRNAs; biomarker discovery; uveal melanoma; colorectal cancer; exosomes; liquid biopsy; transcriptomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Initially considered as splicing errors or transcripts originating from “junk DNA”, non-coding RNAs (ncRNAs) are now recognized as key actors of cellular physiology and pathology. The new millennium brought to light the existence of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). The results of the Human Genome Project, which was published in 2001, showed that about 85–90% of our genome is transcribed in RNA, even though only proteins cover about 1.2% of the entire genome. Since this groundbreaking discovery, various articles have reported on lncRNAs and circRNAs, showing that these molecules play a crucial role in cells as epigenetic regulators of almost all biological processes, similar to the already known microRNAs (miRNAs). Several studies have shown that while ncRNAs are fundamental in cell physiology, both at the intracellular and extracellular levels, they are also dysregulated in pathological tissues and body fluids, paving the way for their application in clinical practice as therapeutic targets and diagnostic/prognostic biomarkers.

This Special Issue will describe the current knowledge on ncRNAs (including miRNAs, lncRNAs, and circRNAs) in physiological and pathological processes, including the onset and progression of diseases. We welcome research articles and reviews on altered expression in tissues or body fluids, polymorphisms, or splicing variants of ncRNAs that are associated with specific disorders.

Dr. Marco Ragusa
Dr. Cristina Barbagallo
Guest Editors

Manuscript Submission Information

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Keywords

  • non-coding RNAs
  • microRNAs
  • long non-coding RNAs
  • circular RNAs
  • biomarkers
  • polymorphisms
  • cancer
  • degenerative diseases
  • therapy

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Published Papers (5 papers)

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Research

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19 pages, 2723 KiB  
Article
miRNA Signatures in Alveolar Macrophages Related to Cigarette Smoke: Assessment and Bioinformatics Analysis
by Davida Mirra, Renata Esposito, Giuseppe Spaziano, Concetta Rafaniello, Francesca Panico, Antonio Squillante, Maddalena Falciani, Diana Marisol Abrego-Guandique, Eleonora Caiazzo, Luca Gallelli, Erika Cione and Bruno D’Agostino
Int. J. Mol. Sci. 2025, 26(3), 1277; https://doi.org/10.3390/ijms26031277 - 1 Feb 2025
Viewed by 239
Abstract
 Cigarette smoke (CS) is a driver of many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. [...] Read more.
 Cigarette smoke (CS) is a driver of many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several regulatory pathways. Previously, we monitored the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p, and 106a-5p in AMs derived from the bronchoalveolar lavage (BAL) of subjects with NSCLC, COPD, and smoker and non-smoker control groups. Here, we investigated the capability of CS conditionate media to modulate the abovementioned miRNAs in primary AMs obtained in the same 43 sex-matched subjects. The expressions of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p were assessed before and after in vitro CS exposure by RT-PCR. In addition, a comprehensive bioinformatic analysis of miRNAs KEGGS and PPI linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is worth noting that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both smokers and non-smokers, 106a-5p in non-smokers, and 20a-5p in smokers, shifted towards those found in individuals with COPD, suggesting them as a risk factor in developing this lung condition. Moreover, CS-focused sub-analysis identified miRNA which exhibited CS-dependent pattern and modulated mRNA involved in the immune system or AMs property regulation. In conclusion, our study uncovered miRNA signatures in AMs exposed to CS, indicating that CS might modify epigenetic patterns that contribute to macrophage activation and lung disease onset and progression. Full article
(This article belongs to the Special Issue Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease)
16 pages, 7913 KiB  
Article
Identification and Evaluation of Hub Long Non-Coding RNAs and mRNAs in PM2.5-Induced Lung Cell Injury
by Jing Sui, Yanni Zhang, Linjie Zhang and Hui Xia
Int. J. Mol. Sci. 2025, 26(3), 911; https://doi.org/10.3390/ijms26030911 - 22 Jan 2025
Viewed by 427
Abstract
Exposure to air pollution, especially fine particulate matter (PM2.5), is closely linked to various adverse health effects, particularly in the respiratory system. The present study was designed to investigate the lncRNA–mRNA interactions in PM2.5-induced lung cell injury using weighted gene co-expression network analysis [...] Read more.
Exposure to air pollution, especially fine particulate matter (PM2.5), is closely linked to various adverse health effects, particularly in the respiratory system. The present study was designed to investigate the lncRNA–mRNA interactions in PM2.5-induced lung cell injury using weighted gene co-expression network analysis (WGCNA). We downloaded the gene expression data of GSE138870 from the Gene Expression Omnibus (GEO) database and screened for differentially expressed lncRNAs and mRNAs. We constructed co-expression modules with WGCNA. Furthermore, functional enrichment analysis was also performed. We also constructed lncRNA–mRNA co-expression networks and lncRNA–mRNA-pathway networks to identify key regulatory relationships. The results revealed several modules significantly correlated with PM2.5-induced lung injury, such as the turquoise and blue modules. Genes within these modules were enriched in pathways related to signal transduction, metabolism, and cancer. Hub lncRNAs in the turquoise module, including LOC100129034 and CROCCP2, were found to be co-expressed with mRNAs involved in apoptosis and proliferation regulation. In the blue module, lnc-CLVS2-2 and GARS1-DT were connected to genes related to cell migration, invasion, and lung injury. These findings contribute novel perspectives to the molecular mechanisms involved in PM2.5-induced lung injury and suggest that WGCNA could be a valuable tool for predicting and understanding this disease process. Full article
(This article belongs to the Special Issue Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease)
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11 pages, 1825 KiB  
Article
The Expression of miR-211-5p in Sentinel Lymph Node Metastases of Malignant Melanoma Is a Potential Marker for Poor Prognosis
by Rose Kathrin Caroline Moritz, Nicole Ebelt, Tina Rattay, Jovine Ehrenreich, Cord Sunderkötter and Dennis Gerloff
Int. J. Mol. Sci. 2024, 25(19), 10859; https://doi.org/10.3390/ijms251910859 - 9 Oct 2024
Viewed by 930
Abstract
Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and [...] Read more.
Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and its potential use as a prognostic biomarker. We performed in situ hybridization for miRNA-211-5p on 109 FFPE melanoma samples from 76 patients, including 31 paired primary tumor/metastasis samples. For validation, we performed in silico analyses of TCGA skin cutaneous melanoma (SKCM) cohort. High miR-211-5p expression was more frequent in primary tumors (70.8%) compared to metastases (39.3%). In metastases, it was associated with a significantly worse overall survival. Data from TCGA SKCM cohort confirmed that high miR-211-5p expression in melanoma metastases, but not primary tumors, is associated with worse overall survival. MiR-211-5p expression in metastases is associated with a shorter survival, emphasizing the potential of miR-211-5p as a risk predictor for a less favorable clinical outcome in metastatic disease. In situ hybridization could be implemented in a routine laboratory workflow and can be performed on diagnostic tissue. Full article
(This article belongs to the Special Issue Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease)
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22 pages, 4365 KiB  
Article
Extracellular RNAs from Whole Urine to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia
by Michele Stella, Giorgio Ivan Russo, Rosario Leonardi, Daniela Carcò, Giuseppe Gattuso, Luca Falzone, Carmen Ferrara, Angela Caponnetto, Rosalia Battaglia, Massimo Libra, Davide Barbagallo, Cinzia Di Pietro, Salvatore Pernagallo, Cristina Barbagallo and Marco Ragusa
Int. J. Mol. Sci. 2024, 25(18), 10079; https://doi.org/10.3390/ijms251810079 - 19 Sep 2024
Viewed by 1616
Abstract
RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease’s initiation, progression, and treatment [...] Read more.
RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease’s initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis. Full article
(This article belongs to the Special Issue Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease)
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Review

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20 pages, 958 KiB  
Review
mirSNPs as Potential Colorectal Cancer Biomarkers: A Systematic Review
by Katiusse Alves dos Santos, Lourdes Maria Costa Alves de Sousa, Karla Simone Costa de Souza, Olalla Maroñas Amigo, André Ducati Luchessi and Vivian Nogueira Silbiger
Int. J. Mol. Sci. 2024, 25(23), 12975; https://doi.org/10.3390/ijms252312975 - 3 Dec 2024
Viewed by 795
Abstract
Colorectal cancer (CRC) is the third most common neoplasm in the world and the second with the highest mortality rate. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes known as mirSNPs may be related to dysregulated miRNA expression in several neoplasms. This systematic [...] Read more.
Colorectal cancer (CRC) is the third most common neoplasm in the world and the second with the highest mortality rate. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes known as mirSNPs may be related to dysregulated miRNA expression in several neoplasms. This systematic review aims to investigate studies that investigate SNPs located in regions of miRNA genes that influence their expression and are associated with CRC, as well as their potential as biomarkers for the disease, based on the available literature. For this, searches were performed in public databases, including MEDLINE/PubMed, Embase, Web of Science, and Scopus. The rigorous review of the PRISMA 2020 guidelines and the methodological quality of these studies was assessed using the Newcastle–Ottawa scale and the Mixed Methods Assessment Tool. Of the 175 studies identified, 26 were considered eligible: 18 of them highlighted mirSNPs as potential biomarkers of risk and prognosis for CRC; 4 studies suggested a protective role; 1 study linked mirSNPs to treatment; 3 studies found no relevant evidence. These results highlight the importance of conducting further research on the topic, given the potential of these biomarkers to contribute to risk assessment, prognosis, and the development of therapeutic strategies for patients with CRC. Full article
(This article belongs to the Special Issue Roles and Mechanisms of Non-Coding RNAs in Human Health and Disease)
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