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The MicroRNAs in the Pathophysiology of Chronic Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 8592

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Special Issue Editors

Dr. Mauro Finicelli

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Guest Editor

Research Institute on Terrestrial Ecosystems (IRET), National Research Council of Italy (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
Interests: stem cell; bioactive molecules; pulmonary disease; aging related disease; senescence; miRNA
Special Issues, Collections and Topics in MDPI journals

Dr. Tiziana Squillaro

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Guest Editor

Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, Via Pansini, 80131 Naples, Italy
Interests: stem cells; cell culture; apoptosis; authophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules. MiRNAs block translation and/or promote mRNA degradation by binding to the 3′-untranslated regions of messenger RNAs. A consistent body of literature has acknowledged the key role of miRNAs in a wide range of physiological and pathophysiological processes, including cancer, cardiovascular diseases, metabolic disorders and neurodegenerative diseases.

MiRNAs target multiple mRNAs that could be altered in disease conditions. This makes these molecules interesting candidates as therapeutics or as targets of therapeutics. Advances in RNA chemistry and delivery technologies, including nanoparticle systems, have now enabled the first miRNA-based agents to move into the clinic. MiRNAs can also be useful tools to dissect the molecular pathways involved in disease progression. Much evidence has shown that natural products such as paclitaxel, curcumin, resveratrol, genistein and epigallocatechin-3-gallate exert their anti-proliferative and/or pro-apoptotic effects through regulating one or more miRNAs.

Moreover, the presence of circulating miRNAs in serum, plasma and other body fluids has meant that their potential usefulness as biomarkers for different diseases could be explored. As most studies have focused on the association between the changes in miRNAs and the clearly defined stage of a disease, it is intriguing to investigate both the physiological and miRNA changes in patients suffering with many chronic diseases.

This Special Issue welcomes original research and critical reviews on the role of miRNAs (long non-coding RNAs; circular-RNAs are also accepted) in physiological and pathological processes. The topics of this Special Issue include but are not limited to the following: i. the molecular mechanisms and regulatory pathways influenced by non-coding RNAs; ii. the prognostic and therapeutic relevance of these molecules and iii. their role in chronic diseases (such as cancer, cardiovascular disease, neurological diseases, immune-related diseases and metabolic disorders) and in response to unhealthy habits and environmental stressors.

Dr. Mauro Finicelli
Dr. Tiziana Squillaro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

miRNA
lncRNA
circRNA
circulating miRNAs
cancer
cardiovascular disease
neurological diseases
metabolic diseases
immunological diseases
nutraceutical
nanodelivery systems
environmental stressors
unhealthy habits

Published Papers (6 papers)

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Research

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21 pages, 6676 KiB

Open AccessArticle

The Role of microRNAs in Gene Expression and Signaling Response of Tumor Cells to an Acidic Environment

by Anne Riemann, Mandy Rauschner, Sarah Reime and Oliver Thews

Int. J. Mol. Sci. 2023, 24(23), 16919; https://doi.org/10.3390/ijms242316919 - 29 Nov 2023

Viewed by 664

Abstract

Many tumors are characterized by marked extracellular acidosis due to increased glycolytic metabolism, which affects gene expression and thereby tumor biological behavior. At the same time, acidosis leads to altered expression of several microRNAs (Mir7, Mir183, Mir203, Mir215). The aim of this study was to analyze whether the acidosis-induced changes in cytokines and tumor-related genes are mediated via pH-sensitive microRNAs. Therefore, the expression of Il6, Nos2, Ccl2, Spp1, Tnf, Acat2, Aox1, Crem, Gls2, Per3, Pink1, Txnip, and Ypel3 was examined in acidosis upon simultaneous transfection with microRNA mimics or antagomirs in two tumor lines in vitro and in vivo. In addition, it was investigated whether microRNA expression in acidosis is affected via known pH-sensitive signaling pathways (MAPK, PKC, PI3K), via ROS, or via altered intracellular Ca²⁺ concentration. pH-dependent microRNAs were shown to play only a minor role in modulating gene expression. Individual genes (e.g., Ccl2, Txnip, Ypel3) appear to be affected by Mir183, Mir203, or Mir215 in acidosis, but these effects are cell line-specific. When examining whether acid-dependent signaling affects microRNA expression, it was found that Mir203 was modulated by MAPK and ROS, Mir7 was affected by PKC, and Mir215 was dependent on the intracellular Ca²⁺ concentration. Mir183 could be increased by ROS scavenging. These correlations could possibly result in new therapeutic approaches for acidotic tumors. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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13 pages, 2050 KiB

Open AccessArticle

Identification of MicroRNAs Associated with Prediabetic Status in Obese Women

by Leona Kovac, Thilo Speckmann, Markus Jähnert, Pascal Gottmann, Louise Fritsche, Hans-Ulrich Häring, Andreas L. Birkenfeld, Andreas Fritsche, Annette Schürmann and Meriem Ouni

Int. J. Mol. Sci. 2023, 24(21), 15673; https://doi.org/10.3390/ijms242115673 - 27 Oct 2023

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Abstract

MicroRNAs (miRNAs) recently emerged as means of communication between insulin-sensitive tissues to mediate diabetes development and progression, and as such they present a valuable proxy for epigenetic alterations associated with type 2 diabetes. In order to identify miRNA markers for the precursor of diabetes called prediabetes, we applied a translational approach encompassing analysis of human plasma samples, mouse tissues and an in vitro validation system. MiR-652-3p, miR-877-5p, miR-93-5p, miR-130a-3p, miR-152-3p and let-7i-5p were increased in plasma of women with impaired fasting glucose levels (IFG) compared to those with normal fasting glucose and normal glucose tolerance (NGT). Among these, let-7i-5p and miR-93-5p correlated with fasting blood glucose levels. Human data were then compared to miRNome data obtained from islets of Langerhans and adipose tissue of 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and liver fat content. Similar to human plasma, let-7i-5p was increased in adipose tissue and islets of Langerhans of diabetes-prone mice. As predicted by the in silico analysis, overexpression of let-7i-5p in the rat β-cell line INS-1 832/12 resulted in downregulation of insulin signaling pathway components (Insr, Rictor, Prkcb, Clock, Sos1 and Kcnma1). Taken together, our integrated approach highlighted let-7i-5p as a potential regulator of whole-body insulin sensitivity and a novel marker of prediabetes in women. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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23 pages, 3717 KiB

Open AccessArticle

Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients

by Maram Almohaywi, Bruna M. Sugita, Ariana Centa, Aline S. Fonseca, Valquiria C. Antunes, Paolo Fadda, Ciaran M. Mannion, Tomilowo Abijo, Stuart L. Goldberg, Michael C. Campbell, Robert L. Copeland, Yasmine Kanaan and Luciane R. Cavalli

Int. J. Mol. Sci. 2023, 24(17), 13046; https://doi.org/10.3390/ijms241713046 - 22 Aug 2023

Cited by 2 | Viewed by 2052

Abstract

Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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12 pages, 4915 KiB

Open AccessArticle

MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6

by I-Ting Lin, Yu-Han Lin, Wei-Shiung Lian, Feng-Sheng Wang and Re-Wen Wu

Int. J. Mol. Sci. 2023, 24(11), 9158; https://doi.org/10.3390/ijms24119158 - 23 May 2023

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Abstract

Spinal epidural fibrosis is one of the typical features attributable to failed back surgery syndrome, with excessive scar development in the dura and nerve roots. The microRNA-29 family (miR-29s) has been found to act as a fibrogenesis-inhibitory factor that reduces fibrotic matrix overproduction in various tissues. However, the mechanistic basis of miRNA-29a underlying the overabundant fibrotic matrix synthesis in spinal epidural scars post-laminectomy remained elusive. This study revealed that miR-29a attenuated lumbar laminectomy-induced fibrogenic activity, and epidural fibrotic matrix formation was significantly lessened in the transgenic mice (miR-29aTg) as compared with wild-type mice (WT). Moreover, miR-29aTg limits laminectomy-induced damage and has also been demonstrated to detect walking patterns, footprint distribution, and moving activity. Immunohistochemistry staining of epidural tissue showed that miR-29aTg was a remarkably weak signal of IL-6, TGF-β1, and DNA methyltransferase marker, Dnmt3b, compared to the wild-type mice. Taken together, these results have further strengthened the evidence that miR-29a epigenetic regulation reduces fibrotic matrix formation and spinal epidural fibrotic activity in surgery scars to preserve the integrity of the spinal cord core. This study elucidates and highlights the molecular mechanisms that reduce the incidence of spinal epidural fibrosis, eliminating the risk of gait abnormalities and pain associated with laminectomy. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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Review

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22 pages, 2025 KiB

Open AccessReview

Circulating microRNAs in Cancer: A 5-Year Update with a Focus on Breast and Lung Cancers

by Dario Siniscalco, Umberto Galderisi, Gianfranco Peluso and Mauro Finicelli

Int. J. Mol. Sci. 2024, 25(6), 3140; https://doi.org/10.3390/ijms25063140 - 8 Mar 2024

Viewed by 977

Abstract

Circulating microRNAs (c-miRNAs) are non-coding RNAs found in different bodily fluids and are highly investigated for their prognostic potential and biological role in cancer. In this narrative review, we provide an update of the last five years’ published papers (2018–2023) on PubMed about c-miRNAs in cancer research. We aim to capture the latest research interests in terms of the highly studied cancers and the insights about c-miRNAs. Our analysis revealed that more than 150 papers focusing on c-miRNAs and cancer were published in the last five years. Among these, there was a high prevalence of papers on breast cancer (BC) and lung cancer (LC), which are estimated to be the most diagnosed cancers globally. Thus, we focus on the main evidence and research trends about c-miRNAs in BC and LC. We report evidence of the effectiveness of c-miRNAs in hot topics of cancer research, such as, early detection, therapeutic resistance, recurrence risk and novel detection platform approaches. Moreover, we look at the deregulated c-miRNAs shared among BC and LC papers, focusing on miR-21 and miR-145. Overall, these data clearly indicate that the role of c-miRNAs in cancer is still a hot topic for oncologic research and that blood is the most investigated matrix. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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23 pages, 1272 KiB

Open AccessReview

Interactions between circRNAs and miR-141 in Cancer: From Pathogenesis to Diagnosis and Therapy

by Małgorzata Guz, Witold Jeleniewicz and Marek Cybulski

Int. J. Mol. Sci. 2023, 24(14), 11861; https://doi.org/10.3390/ijms241411861 - 24 Jul 2023

Cited by 1 | Viewed by 1407

Abstract

The function of non-coding RNAs (ncRNAs) in the pathogenesis and development of cancer is indisputable. Molecular mechanisms underlying carcinogenesis involve the aberrant expression of ncRNAs, including circular RNAs (circRNAs), and microRNAs (miRNAs). CircRNAs are a class of single-stranded, covalently closed RNAs responsible for maintaining cellular homeostasis through their diverse functions. As a part of the competing endogenous RNA (ceRNAs) network, they play a central role in the regulation of accessibility of miRNAs to their mRNA targets. The interplay between these molecular players is based on the primary role of circRNAs that act as miRNAs sponges, and the circRNA/miRNA imbalance plays a central role in different pathologies including cancer. Herein, we present the latest state of knowledge about interactions between circRNAs and miR-141, a well-known member of the miR-200 family, in malignant transformation, with emphasis on the biological role of circRNA/miR-141/mRNA networks as a future target for novel anti-cancer therapies. Full article

(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)

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