Non-coding RNAs in Health and Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 48420

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Guest Editor
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
Interests: cancer cell biology; microRNAs; pediatric brain tumors; metabolic diseases
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Dear Colleagues,

The idea that genetic information travelling towards proteins has represented, for many years, the “central dogma” of molecular biology. However, proteins are encoded only from the 2% of human genome, while the widest part is represented by non-coding transcriptome. Non-coding RNAs (nc-RNAs) indeed comprise the largest part of the transcriptional production of the human genome, playing pivotal roles, both in health and disease processes. Some of them, such as microRNAs and circular RNAs (circRNAs), are highly conserved across species; while others, such as long non-coding RNAs (lnc-RNAs), lack conservation. Nc-RNAs are especially involved in regulatory functions; moreover, they can interact with each other to regulate stability or abundance. These interactions are of the utmost importance in the regulation of many different cellular programs. As a result, their dysregulation, as well as a perturbation of their interactions, may have striking consequences. In addition, more recently, nc-RNAs have also been described in the extracellular compartment, therefore inferring that they mediate cell-to-cell communication and act as disease-specific diagnostic, prognostic and treatment response biomarkers.

This Special Issue aims to focus on the role of the different species of nc-RNAs in controlling pivotal biological mechanisms, such as gene expression and developmental pathways, as well as on analyzing their dysregulation in the context of many different human diseases, spanning from metabolic, neurological and cardiovascular diseases to cancer. Moreover, it will concentrate on the possibility of using these molecules as biomarkers, with the potential to use liquid biopsies in modern precision medicine. Original research articles and comprehensive reviews are both welcomed here.

Dr. Giuseppina Catanzaro
Guest Editor

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Keywords

  • non-coding RNAs
  • cellular pathways
  • developmental pathways
  • gene expression
  • metabolic diseases
  • neurological diseases
  • cardiovascular diseases
  • cancer
  • liquid biopsy
  • biomarkers

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Published Papers (14 papers)

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Editorial

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2 pages, 182 KiB  
Editorial
Non-Coding RNAs in Health and Disease: Editorial
by Giuseppina Catanzaro
Biomedicines 2023, 11(1), 14; https://doi.org/10.3390/biomedicines11010014 - 21 Dec 2022
Cited by 1 | Viewed by 1178
Abstract
Non-coding RNAs (ncRNAs) represent the largest part of the transcriptional production of the human genome and play key roles in health and disease processes [...] Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)

Research

Jump to: Editorial, Review

21 pages, 2185 KiB  
Article
DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile
by Oliver Treeck, Florian Weber, Juergen Fritsch, Maciej Skrzypczak, Susanne Schüler-Toprak, Christa Buechler and Olaf Ortmann
Biomedicines 2022, 10(7), 1727; https://doi.org/10.3390/biomedicines10071727 - 18 Jul 2022
Cited by 4 | Viewed by 2056
Abstract
Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial [...] Read more.
Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial adenocarcinoma using in silico and different in vitro approaches. Initial analysis of open-source data revealed DSCAM-AS1 overexpression in endometrial cancer (EC) (p < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, p < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene PRL and with expression of ERα and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ERα-negative HEC-1B cells and reduced their growth and the expression of proliferation activators like NOTCH1, PTK2 and EGR1. DSCAM-AS1 knockdown triggered an anti-tumoral transcriptome response as revealed by Affymetrix microarray analysis, emerging from down-regulation of tumor-promoting genes and induction of tumor-suppressive networks. Finally, several genes regulated upon DSCAM-AS1 silencing in vitro were found to be inversely correlated with this lncRNA in EC tissues. This study clearly suggests an oncogenic function of DSCAM-AS1 in endometrial adenocarcinoma via activation of a tumor-promoting transcriptome profile. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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13 pages, 3335 KiB  
Article
miR-195-5p Regulates Tight Junctions Expression via Claudin-2 Downregulation in Ulcerative Colitis
by Viviana Scalavino, Emanuele Piccinno, Antonio Lacalamita, Angela Tafaro, Raffaele Armentano, Gianluigi Giannelli and Grazia Serino
Biomedicines 2022, 10(4), 919; https://doi.org/10.3390/biomedicines10040919 - 16 Apr 2022
Cited by 14 | Viewed by 2910
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of [...] Read more.
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of intestinal permeability and barrier function. We identified 18 dysregulated miRNAs in intestinal epithelial cells (IECs) from the ulcerative colitis (UC) mice model and control mice. Among them, down-regulated miR-195-5p targeted claudin-2 (CLDN2) and was involved in impaired barrier function. CLDN2 expression levels were increased in UC mice models and negatively correlated with miR-195-5p expression. We demonstrated that gain-of-function of miR-195-5p in colonic epithelial cell lines decreased the CLDN2 levels. This modulation, in turn, downregulated claudin-1 (CLDN1) expression at protein level but not that of occludin. Our data support a previously unreported role of miR-195-5p in intestinal tight junctions’ regulation and suggest a potential pharmacological target for new therapeutic approaches in IBD. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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17 pages, 3277 KiB  
Article
Testicular “Inherited Metabolic Memory” of Ancestral High-Fat Diet Is Associated with Sperm sncRNA Content
by Luís Crisóstomo, Matthieu Bourgery, Luís Rato, João F. Raposo, Rachel L. Batterham, Noora Kotaja and Marco G. Alves
Biomedicines 2022, 10(4), 909; https://doi.org/10.3390/biomedicines10040909 - 15 Apr 2022
Cited by 11 | Viewed by 3215
Abstract
Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular “inherited metabolic memory” [...] Read more.
Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular “inherited metabolic memory” of ancestral HFD, using a transgenerational rodent model. Male founders were fed a standard chow for 200 days (CTRL), HFD for 200 days (HFD), or standard chow for 60 days followed by HFD for 140 days (HFDt). The male offspring and grand-offspring were fed standard chow for 200 days. The sncRNA sequencing from epidydimal spermatozoa revealed signatures associated with testicular metabolic plasticity in HFD-exposed mice and in the unexposed progeny. Sperm tRNA-derived RNA (tsRNA) and repeat-derived small RNA (repRNA) content were specially affected by HFDt and in the offspring of HFD and HFDt mice. The grand-offspring of HFD and HFDt mice showed lower sperm counts than CTRL descendants, whereas the sperm miRNA content was affected. Although the causality between sperm sncRNAs content and transgenerational epigenetic inheritance of HFD-related traits remains elusive, our results suggest that sperm sncRNA content is influenced by ancestral exposure to HFD, contributing to the sperm epigenome up to the grand-offspring. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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12 pages, 1519 KiB  
Article
Origins and Function of VL30 lncRNA Packaging in Small Extracellular Vesicles: Implications for Cellular Physiology and Pathology
by Stefania Mantziou and Georgios S. Markopoulos
Biomedicines 2021, 9(11), 1742; https://doi.org/10.3390/biomedicines9111742 - 22 Nov 2021
Cited by 4 | Viewed by 1815
Abstract
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles [...] Read more.
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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15 pages, 3731 KiB  
Article
Network Analysis Integrating microRNA Expression Profiling with MRI Biomarkers and Clinical Data for Prostate Cancer Early Detection: A Proof of Concept Study
by Valeria Panebianco, Paola Paci, Martina Pecoraro, Federica Conte, Giorgia Carnicelli, Zein Mersini Besharat, Giuseppina Catanzaro, Elena Splendiani, Alessandro Sciarra, Lorenzo Farina, Carlo Catalano and Elisabetta Ferretti
Biomedicines 2021, 9(10), 1470; https://doi.org/10.3390/biomedicines9101470 - 14 Oct 2021
Cited by 7 | Viewed by 2798
Abstract
The MRI of the prostate is the gold standard for the detection of clinically significant prostate cancer (csPCa). Nonetheless, MRI still misses around 11% of clinically significant disease. The aim was to comprehensively integrate tissue and circulating microRNA profiling, MRI biomarkers and clinical [...] Read more.
The MRI of the prostate is the gold standard for the detection of clinically significant prostate cancer (csPCa). Nonetheless, MRI still misses around 11% of clinically significant disease. The aim was to comprehensively integrate tissue and circulating microRNA profiling, MRI biomarkers and clinical data to implement PCa early detection. In this prospective cohort study, 76 biopsy naïve patients underwent MRI and MRI directed biopsy. A sentinel sample of 15 patients was selected for a pilot molecular analysis. Weighted gene coexpression network analysis was applied to identify the microRNAs drivers of csPCa. MicroRNA–target gene interaction maps were constructed, and enrichment analysis performed. The ANOVA on ranks test and ROC analysis were performed for statistics. Disease status was associated with the underexpression of the miRNA profiled; a correlation was found with ADC (r = −0.51, p = 0.02) and normalized ADC values (r = −0.64, p = 0.002). The overexpression of miRNAs from plasma was associated with csPCa (r = 0.72; p = 0.02), and with PI-RADS assessment score (r = 0.73; p = 0.02); a linear correlation was found with biomarkers of diffusion and perfusion. Among the 800 profiled microRNA, eleven were identified as correlating with PCa, among which miR-548a-3p, miR-138-5p and miR-520d-3p were confirmed using the RT-qPCR approach on an additional cohort of ten subjects. ROC analysis showed an accuracy of >90%. Provided an additional validation set of the identified miRNAs on a larger cohort, we propose a diagnostic paradigm shift that sees molecular data and MRI biomarkers as the prebiopsy triage of patients at risk for PCa. This approach will allow for accurate patient allocation to biopsy, and for stratification into risk group categories, reducing overdiagnosis and overtreatment. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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17 pages, 3249 KiB  
Article
The lncRNA 44s2 Study Applicability to the Design of 45-55 Exon Skipping Therapeutic Strategy for DMD
by Elena Gargaun, Sestina Falcone, Guilhem Solé, Julien Durigneux, Andoni Urtizberea, Jean Marie Cuisset, Sofia Benkhelifa-Ziyyat, Laura Julien, Anne Boland, Florian Sandron, Vincent Meyer, Jean François Deleuze, David Salgado, Jean-Pierre Desvignes, Christophe Béroud, Anatole Chessel, Alexia Blesius, Martin Krahn, Nicolas Levy, France Leturcq and France Pietri-Rouxeladd Show full author list remove Hide full author list
Biomedicines 2021, 9(2), 219; https://doi.org/10.3390/biomedicines9020219 - 20 Feb 2021
Cited by 6 | Viewed by 4205
Abstract
In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are [...] Read more.
In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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15 pages, 955 KiB  
Article
Expression of Circulating MicroRNAs Linked to Bone Metabolism in Chronic Kidney Disease-Mineral and Bone Disorder
by Maria P. Yavropoulou, Vasilios Vaios, Polyzois Makras, Panagiotis Georgianos, Anastasios Batas, Dimitrios Tsalikakis, Alexandros Tzallas, Georgios Ntritsos, Stefanos Roumeliotis, Theodoros Eleftheriadis and Vassilios Liakopoulos
Biomedicines 2020, 8(12), 601; https://doi.org/10.3390/biomedicines8120601 - 12 Dec 2020
Cited by 9 | Viewed by 3127
Abstract
The pathophysiology of chronic kidney disease–mineral and bone disorder (CKD-MBD) is complex and multifactorial. Recent studies have identified a link between microRNAs (miRNAs) and bone loss. In this study, we investigated the expression of miRNAs in CKD-MBD. In this case-control study, we included [...] Read more.
The pathophysiology of chronic kidney disease–mineral and bone disorder (CKD-MBD) is complex and multifactorial. Recent studies have identified a link between microRNAs (miRNAs) and bone loss. In this study, we investigated the expression of miRNAs in CKD-MBD. In this case-control study, we included thirty patients with CKD-MBD (cases) and 30 age- and gender-matched healthy individuals (controls). Bone mineral density (BMD) and trabecular bone score (TBS) evaluation was performed with dual X-ray absorptiometry. The selected panel of miRNAs included: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3; hsa-miRNA-124-3p; hsa-miRNA-2861. The majority of cases had low BMD values. The relative expression of miRNA-21-5p was 15 times lower [fold regulation (FR): −14.7 ± 8.1, p = 0.034), miRNA-124-3p, 6 times lower (FR: −5.9 ± 4, p = 0.005), and miRNA-23a-3p, 4 times lower (FR: −3.8 ± 2.0, p = 0.036) in cases compared to controls. MiRNA-23a-3p was significantly and inversely correlated with TBS, adjusted for calcium metabolism and BMD values (beta = −0.221, p = 0.003, 95% CI −0.360, −0,081) in cases. In a receiver operating characteristic (ROC) analysis, expression of miRNA-124-3p demonstrated 78% sensitivity and 83% specificity in identifying CKD patents with osteoporosis. Serum expression of miRNAs related to osteoblasts (miRNA-23a-3p) and osteoclasts (miRNA-21-5p, miRNA-124-3p) is significantly altered in patients with CKD-MBD. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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10 pages, 1014 KiB  
Article
miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19
by Alessandro Matarese, Jessica Gambardella, Celestino Sardu and Gaetano Santulli
Biomedicines 2020, 8(11), 462; https://doi.org/10.3390/biomedicines8110462 - 30 Oct 2020
Cited by 115 | Viewed by 7196
Abstract
The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Here, we focused on the study of microRNAs that specifically target TMPRSS2. Through a [...] Read more.
The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Here, we focused on the study of microRNAs that specifically target TMPRSS2. Through a bioinformatic approach, we identified miR-98-5p as a suitable candidate. Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein. Taken together, our findings indicate that TMPRSS2 represents a valid target in COVID-19 treatment, which may be achieved by specific non-coding-RNA approaches. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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Review

Jump to: Editorial, Research

28 pages, 1587 KiB  
Review
Small Noncoding RNAs in Reproduction and Infertility
by Qifan Zhu, Jane Allyn Kirby, Chen Chu and Lan-Tao Gou
Biomedicines 2021, 9(12), 1884; https://doi.org/10.3390/biomedicines9121884 - 12 Dec 2021
Cited by 17 | Viewed by 4875
Abstract
Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical [...] Read more.
Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction. Advanced technologies have revealed the dynamic expression and diverse functions of sncRNAs during mammalian germ cell development. Mounting evidence indicates sncRNAs in sperm, especially microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs), are sensitive to environmental changes and mediate the inheritance of paternally acquired metabolic and mental traits. Here, we review the critical roles of sncRNAs in mammalian germ cell development. Furthermore, we highlight the functions of sperm-borne sncRNAs in epigenetic inheritance. We also discuss evidence supporting sncRNAs as promising biomarkers for fertility and embryo quality in addition to the present limitations of using sncRNAs for infertility diagnosis and treatment. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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11 pages, 263 KiB  
Review
miRNAs and lncRNAs: Potential Non-Invasive Biomarkers for Endometriosis
by Ioana Maria Maier and Adrian Cornel Maier
Biomedicines 2021, 9(11), 1662; https://doi.org/10.3390/biomedicines9111662 - 11 Nov 2021
Cited by 15 | Viewed by 2415
Abstract
Many studies have tried to understand the mechanism of endometriosis and its manner of manifestation. However, the only method of diagnosis considered as the gold standard in endometriosis is an invasive method called exploratory laparoscopy. Hence, there is a need to identify non-invasive [...] Read more.
Many studies have tried to understand the mechanism of endometriosis and its manner of manifestation. However, the only method of diagnosis considered as the gold standard in endometriosis is an invasive method called exploratory laparoscopy. Hence, there is a need to identify non-invasive or minimally invasive methods to minimize patients’ suffering, thus increasing their addressability at the earliest possible staging of the disease, and to diagnose this condition as soon as possible. miRNAs (microRNAs) and lncRNAs (long-noncoding RNAs) are potential non-invasive diagnostic methods for endometriosis. Multiple clinical trials indicate that miRNA can be used as a non-invasive method in the diagnosis and differentiation of endometriosis stages. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
16 pages, 692 KiB  
Review
Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications
by Rosaria Varì, Beatrice Scazzocchio, Tiziana Filardi, Anna Citarella, Maria Bellenghi, Roberta Masella and Carmela Santangelo
Biomedicines 2021, 9(11), 1509; https://doi.org/10.3390/biomedicines9111509 - 20 Oct 2021
Cited by 5 | Viewed by 2530
Abstract
In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as [...] Read more.
In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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38 pages, 3947 KiB  
Review
The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer
by Ekaterina Mikhailovna Stasevich, Matvey Mikhailovich Murashko, Lyudmila Sergeevna Zinevich, Denis Eriksonovich Demin and Anton Markovich Schwartz
Biomedicines 2021, 9(8), 921; https://doi.org/10.3390/biomedicines9080921 - 30 Jul 2021
Cited by 15 | Viewed by 4438
Abstract
Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes [...] Read more.
Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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14 pages, 571 KiB  
Review
MicroRNA Modulation by Dietary Supplements in Obesity
by Tiziana Filardi, Claudia Sabato, Carla Lubrano, Carmela Santangelo, Susanna Morano, Andrea Lenzi, Silvia Migliaccio, Elisabetta Ferretti and Giuseppina Catanzaro
Biomedicines 2020, 8(12), 545; https://doi.org/10.3390/biomedicines8120545 - 27 Nov 2020
Cited by 8 | Viewed by 3532
Abstract
The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including [...] Read more.
The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities, contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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