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The MicroRNAs in the Pathophysiology of Chronic Diseases

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 17072

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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
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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

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Keywords

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

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Published Papers (9 papers)

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Research

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21 pages, 6676 KiB  
Article
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 1049
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). [...] Read more.
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  
Article
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
Viewed by 1497
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 [...] Read more.
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  
Article
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 5 | Viewed by 2671
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 [...] Read more.
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  
Article
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
Cited by 1 | Viewed by 1876
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 [...] Read more.
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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29 pages, 443 KiB  
Review
Molecular Morbidity Score–Can MicroRNAs Assess the Burden of Disease?
by Thomas Butler, Matthew G. Davey and Michael J. Kerin
Int. J. Mol. Sci. 2024, 25(15), 8042; https://doi.org/10.3390/ijms25158042 - 24 Jul 2024
Viewed by 933
Abstract
Multimorbidity refers to the presence of two or more chronic diseases and is associated with adverse outcomes for patients. Factors such as an ageing population have contributed to a rise in prevalence of multimorbidity globally; however, multimorbidity is often neglected in clinical guidelines. [...] Read more.
Multimorbidity refers to the presence of two or more chronic diseases and is associated with adverse outcomes for patients. Factors such as an ageing population have contributed to a rise in prevalence of multimorbidity globally; however, multimorbidity is often neglected in clinical guidelines. This is largely because patients with multimorbidity are systematically excluded from clinical trials. Accordingly, there is an urgent need to develop novel biomarkers and methods of prognostication for this cohort of patients. The hallmarks of ageing are now thought to potentiate the pathogenesis of multimorbidity. MicroRNAs are small, regulatory, noncoding RNAs which have been implicated in the pathogenesis and prognostication of numerous chronic diseases; there is a substantial body of evidence now implicating microRNA dysregulation with the different hallmarks of ageing in the aetiology of chronic diseases. This article proposes using the hallmarks of ageing as a framework to develop a panel of microRNAs to assess the prognostic burden of multimorbidity. This putative molecular morbidity score would have many potential applications, including assessing the efficacy of clinical interventions, informing clinical decision making and facilitating wider inclusion of patients with multimorbidity in clinical trials. Full article
(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)
20 pages, 1154 KiB  
Review
The Role of MicroRNAs in the Pathophysiology of Osteoarthritis
by Dariusz Szala, Marta Kopańska, Julia Trojniak, Jarosław Jabłoński, Dorota Hanf-Osetek, Sławomir Snela and Izabela Zawlik
Int. J. Mol. Sci. 2024, 25(12), 6352; https://doi.org/10.3390/ijms25126352 - 8 Jun 2024
Cited by 1 | Viewed by 2325
Abstract
Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis’ development and progression, including secondary osteoarthritis’ underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and [...] Read more.
Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis’ development and progression, including secondary osteoarthritis’ underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and articular apparatus. An increasingly prominent area of research in osteoarthritis regulation is microRNAs (miRNAs), a small, single-stranded RNA molecule that controls gene expression in eukaryotes. We aimed to assess and summarize current knowledge about the mechanisms of the action of miRNAs and their clinical significance. Osteoarthritis (OA) is affected by the interaction between miRNAs and inflammatory processes, as well as cartilage metabolism. MiRNAs also influence cartilage cell apoptosis, contributing to the degradation of the cartilage in OA. Studies have shown that miRNAs may have both an inhibitory and promoting effect on osteoporosis progression through their influence on molecular mechanisms. By identifying these regulators, targeted treatments for osteoarthritis may be developed. In addition, microRNA may also serve as a biomarker for osteoarthritis. By using these biomarkers, the disease could be detected faster, and early intervention can be instituted to prevent mobility loss and slow deterioration. Full article
(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)
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24 pages, 1936 KiB  
Review
The MicroRNAs in the Pathophysiology of Osteoporosis
by Julia Trojniak, Anna Sendera, Agnieszka Banaś-Ząbczyk and Marta Kopańska
Int. J. Mol. Sci. 2024, 25(11), 6240; https://doi.org/10.3390/ijms25116240 - 5 Jun 2024
Cited by 2 | Viewed by 1481
Abstract
Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis’ development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted [...] Read more.
Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis’ development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted to the role that microRNA (miRNA) plays in osteoporosis regulation. A microRNA (miRNA) is a group of small single-stranded RNA molecules involved in regulating gene expression in eukaryotic organisms. As microRNAs (miRNAs) are key regulators of gene expression and can modulate processes related to bone metabolism, they have become increasingly important for studying osteoporosis pathogenesis. The available research suggests that miRNAs play an important role in regulating processes associated with bone metabolism, especially by influencing bone resorption and synthesis. Furthermore, microRNAs can also serve as potential therapeutic targets for osteoporosis, besides being a rapid and specific biomarker. Full article
(This article belongs to the Special Issue The MicroRNAs in the Pathophysiology of Chronic Diseases)
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22 pages, 2025 KiB  
Review
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 1926
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 [...] Read more.
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  
Review
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 5 | Viewed by 1910
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 [...] Read more.
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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