International Journal of Molecular Sciences

Editorial

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3 pages, 182 KiB

Open AccessEditorial

Non-Coding RNAs and Human Diseases: Current Status and Future Perspectives

by Justyna Niderla-Bielińska, Ewa Jankowska-Steifer and Paweł Włodarski

Int. J. Mol. Sci. 2023, 24(14), 11679; https://doi.org/10.3390/ijms241411679 - 20 Jul 2023

Cited by 4 | Viewed by 873

Abstract

Non-coding RNAs (ncRNAs) are a family of RNA molecules that, unlike messenger RNAs, are not templates for protein synthesis but have an essential or regulatory role in this process [...] Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

Research

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11 pages, 1348 KiB

Open AccessArticle

Methylation-Regulated Long Non-Coding RNA Expression in Ulcerative Colitis

by Christopher G. Fenton, Mithlesh Kumar Ray, Wei Meng and Ruth H. Paulssen

Int. J. Mol. Sci. 2023, 24(13), 10500; https://doi.org/10.3390/ijms241310500 - 22 Jun 2023

Cited by 4 | Viewed by 1965

Abstract

Long non-coding RNAs (lncRNAs) have been shown to play a role in the pathogenesis of ulcerative colitis (UC). Although epigenetic processes such as DNA methylation and lncRNA expression are well studied in UC, the importance of the interplay between the two processes has [...] Read more.

Long non-coding RNAs (lncRNAs) have been shown to play a role in the pathogenesis of ulcerative colitis (UC). Although epigenetic processes such as DNA methylation and lncRNA expression are well studied in UC, the importance of the interplay between the two processes has not yet been fully explored. It is, therefore, believed that interactions between environmental factors and epigenetics contribute to disease development. Mucosal biopsies from 11 treatment-naïve UC patients and 13 normal controls were used in this study. From each individual sample, both whole-genome bisulfite sequencing data (WGBS) and lncRNA expression data were analyzed. Correlation analysis between lncRNA expression and upstream differentially methylated regions (DMRs) was used to identify lncRNAs that might be regulated by DMRs. Furthermore, proximal protein-coding genes associated with DMR-regulated lncRNAs were identified by correlating their expression. The study identified UC-associated lncRNAs such as MIR4435-2HG, ZFAS1, IL6-AS1, and Pvt1, which may be regulated by DMRs. Several genes that are involved in inflammatory immune responses were found downstream of DMR-regulated lncRNAs, including SERPINB1, CCL18, and SLC15A4. The interplay between lncRNA expression regulated by DNA methylation in UC might improve our understanding of UC pathogenesis. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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14 pages, 2997 KiB

Open AccessArticle

Circulating MicroRNA Profiling Identifies Distinct MicroRNA Signatures in Acute Ischemic Stroke and Transient Ischemic Attack Patients

by Salman M. Toor, Eman K. Aldous, Aijaz Parray, Naveed Akhtar, Yasser Al-Sarraj, Essam M. Abdelalim, Abdelilah Arredouani, Omar El-Agnaf, Paul J. Thornalley, Sajitha V. Pananchikkal, Ghulam Jeelani Pir, Raheem Ayadathil, Ashfaq Shuaib, Nehad M. Alajez and Omar M. E. Albagha

Int. J. Mol. Sci. 2023, 24(1), 108; https://doi.org/10.3390/ijms24010108 - 21 Dec 2022

Cited by 6 | Viewed by 2294

Abstract

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. [...] Read more.

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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15 pages, 1967 KiB

Open AccessArticle

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro

by Aneta Moskalik, Anna Ratajska, Barbara Majchrzak, Ewa Jankowska-Steifer, Krzysztof Bartkowiak, Mateusz Bartkowiak and Justyna Niderla-Bielińska

Int. J. Mol. Sci. 2022, 23(21), 13193; https://doi.org/10.3390/ijms232113193 - 29 Oct 2022

Cited by 2 | Viewed by 1938

Abstract

Cardiac lymphatic vessel (LyV) remodeling as a contributor to heart failure has not been extensively evaluated in metabolic syndrome (MetS). Our studies have shown structural changes in cardiac LyV in MetS that contribute to the development of edema and lead to myocardial fibrosis. [...] Read more.

Cardiac lymphatic vessel (LyV) remodeling as a contributor to heart failure has not been extensively evaluated in metabolic syndrome (MetS). Our studies have shown structural changes in cardiac LyV in MetS that contribute to the development of edema and lead to myocardial fibrosis. Tissue macrophages may affect LyV via secretion of various substances, including noncoding RNAs. The aim of the study was to evaluate the influence of macrophages modified by miR-31-5p, a molecule that regulates fibrosis and lymphangiogenesis, on lymphatic endothelial cells (LECs) in vitro. The experiments were carried out on the RAW 264.7 macrophage cell line and primary dermal lymphatic endothelial cells. RAW 264.7 macrophages were transfected with miR-31-5p and supernatant from this culture was used for LEC stimulation. mRNA expression levels for genes associated with lymphangiogenesis and fibrosis were measured with qRT-PCR. Selected results were confirmed with ELISA or Western blotting. miR-31-5p-modified RAW 264.7 macrophages secreted increased amounts of VEGF-C and TGF-β and a decreased amount of IGF-1. The supernatant from miR-31-5p-modified RAW 264.7 downregulated the mRNA expression for genes regulating endothelial-to-mesenchymal transition (EndoMT) and fibrosis in LECs. Our results suggest that macrophages under the influence of miR-31-5p show the potential to inhibit LEC-dependent fibrosis. However, more studies are needed to confirm this effect in vivo. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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Review

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17 pages, 971 KiB

Open AccessReview

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment

by Sanjna Das, Joshua Hayden, Travis Sullivan and Kimberly Rieger-Christ

Int. J. Mol. Sci. 2023, 24(2), 964; https://doi.org/10.3390/ijms24020964 - 4 Jan 2023

Cited by 3 | Viewed by 1918

Abstract

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited [...] Read more.

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited supply of BCG and identifying cases likely to recur, it would be advantageous to use molecular biomarkers to determine likelihood of recurrence and treatment response. Here, we review microRNAs (miRNAs) that have shown promise as predictors of BCa recurrence. MiRNAs are also discussed in the context of predicting resistance or susceptibility to BCa treatment. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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32 pages, 2195 KiB

Open AccessReview

Advances of Epigenetic Biomarkers and Epigenome Editing for Early Diagnosis in Breast Cancer

by Pourya Sarvari, Pouya Sarvari, Ivonne Ramírez-Díaz, Frouzandeh Mahjoubi and Karla Rubio

Int. J. Mol. Sci. 2022, 23(17), 9521; https://doi.org/10.3390/ijms23179521 - 23 Aug 2022

Cited by 7 | Viewed by 7302

Abstract

Epigenetic modifications are known to regulate cell phenotype during cancer progression, including breast cancer. Unlike genetic alterations, changes in the epigenome are reversible, thus potentially reversed by epi-drugs. Breast cancer, the most common cause of cancer death worldwide in women, encompasses multiple histopathological [...] Read more.

Epigenetic modifications are known to regulate cell phenotype during cancer progression, including breast cancer. Unlike genetic alterations, changes in the epigenome are reversible, thus potentially reversed by epi-drugs. Breast cancer, the most common cause of cancer death worldwide in women, encompasses multiple histopathological and molecular subtypes. Several lines of evidence demonstrated distortion of the epigenetic landscape in breast cancer. Interestingly, mammary cells isolated from breast cancer patients and cultured ex vivo maintained the tumorigenic phenotype and exhibited aberrant epigenetic modifications. Recent studies indicated that the therapeutic efficiency for breast cancer regimens has increased over time, resulting in reduced mortality. Future medical treatment for breast cancer patients, however, will likely depend upon a better understanding of epigenetic modifications. The present review aims to outline different epigenetic mechanisms including DNA methylation, histone modifications, and ncRNAs with their impact on breast cancer, as well as to discuss studies highlighting the central role of epigenetic mechanisms in breast cancer pathogenesis. We propose new research areas that may facilitate locus-specific epigenome editing as breast cancer therapeutics. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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34 pages, 1491 KiB

Open AccessReview

Using ncRNAs as Tools in Cancer Diagnosis and Treatment—The Way towards Personalized Medicine to Improve Patients’ Health

by Roberto Piergentili, Giuseppe Basile, Cristina Nocella, Roberto Carnevale, Enrico Marinelli, Renato Patrone and Simona Zaami

Int. J. Mol. Sci. 2022, 23(16), 9353; https://doi.org/10.3390/ijms23169353 - 19 Aug 2022

Cited by 27 | Viewed by 3430

Abstract

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that [...] Read more.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular network of crossed interactions (competing endogenous RNA networks, or ceRNET) that fine-tune the gene expression in both health and disease. The alteration of the equilibrium among such interactions can be enough to cause a transition from health to disease, but the opposite is equally true, leading to the possibility of intervening based on these mechanisms to cure human conditions. In this review, we summarize the present knowledge on these mechanisms, illustrating how they can be used for disease treatment, the current challenges and pitfalls, and the roles of environmental and lifestyle-related contributing factors, in addition to the ethical, legal, and social issues arising from their (improper) use. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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31 pages, 2290 KiB

Open AccessReview

Non-Coding RNAs in Tuberculosis Epidemiology: Platforms and Approaches for Investigating the Genome’s Dark Matter

by Ahmad Almatroudi

Int. J. Mol. Sci. 2022, 23(8), 4430; https://doi.org/10.3390/ijms23084430 - 17 Apr 2022

Cited by 12 | Viewed by 6862

Abstract

A growing amount of information about the different types, functions, and roles played by non-coding RNAs (ncRNAs) is becoming available, as more and more research is done. ncRNAs have been identified as potential therapeutic targets in the treatment of tuberculosis (TB), because they [...] Read more.

A growing amount of information about the different types, functions, and roles played by non-coding RNAs (ncRNAs) is becoming available, as more and more research is done. ncRNAs have been identified as potential therapeutic targets in the treatment of tuberculosis (TB), because they may be essential regulators of the gene network. ncRNA profiling and sequencing has recently revealed significant dysregulation in tuberculosis, primarily due to aberrant processes of ncRNA synthesis, including amplification, deletion, improper epigenetic regulation, or abnormal transcription. Despite the fact that ncRNAs may have a role in TB characteristics, the detailed mechanisms behind these occurrences are still unknown. The dark matter of the genome can only be explored through the development of cutting-edge bioinformatics and molecular technologies. In this review, ncRNAs’ synthesis and functions are discussed in detail, with an emphasis on the potential role of ncRNAs in tuberculosis. We also focus on current platforms, experimental strategies, and computational analyses to explore ncRNAs in TB. Finally, a viewpoint is presented on the key challenges and novel techniques for the future and for a wide-ranging therapeutic application of ncRNAs. Full article

(This article belongs to the Special Issue Non-coding RNAs and Human Diseases: Current Status and Future Perspectives)

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