Biomedicines

Editorial

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5 pages, 190 KiB

Open AccessEditorial

miRNAs: From Master Regulators of Gene Expression to Biomarkers Involved in Intercellular Communication

by Elena Levantini and Milena Rizzo

Biomedicines 2024, 12(4), 721; https://doi.org/10.3390/biomedicines12040721 - 25 Mar 2024

Cited by 3 | Viewed by 1598

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that act as master regulators of gene expression, fine-tuning the activity of thousands of genes in our cells, by modulating gene expression at the post-transcriptional level [...] Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

Research

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13 pages, 1220 KiB

Open AccessArticle

MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

by Maria Vincenza Chiantore, Marco Iuliano, Roberta Maria Mongiovì, Fabiola Luzi, Giorgio Mangino, Lorenzo Grimaldi, Luisa Accardi, Gianna Fiorucci, Giovanna Romeo and Paola Di Bonito

Biomedicines 2023, 11(6), 1719; https://doi.org/10.3390/biomedicines11061719 - 15 Jun 2023

Cited by 2 | Viewed by 1425

Abstract

Actinic keratosis (AK) is a carcinoma in situ precursor of cutaneous squamous cell carcinoma (cSCC), the second most common cancer affecting the Caucasian population. AK is frequently present in the sun-exposed skin of the elderly population, UV radiation being the main cause of [...] Read more.

Actinic keratosis (AK) is a carcinoma in situ precursor of cutaneous squamous cell carcinoma (cSCC), the second most common cancer affecting the Caucasian population. AK is frequently present in the sun-exposed skin of the elderly population, UV radiation being the main cause of this cancer, and other risk factors contributing to AK incidence. The dysregulation of microRNAs (miRNAs) observed in different cancers leads to an improper expression of miRNA targets involved in several cellular pathways. The TaqMan Array Human MicroRNA Card assay for miRNA expression profiling was performed in pooled AK compared to healthy skin scraping samples from the same patients. Forty-three miRNAs were modulated in the AK samples. The expression of miR-19b (p < 0.05), -31, -34a (p < 0.001), -126, -146a (p < 0.01), -193b, and -222 (p < 0.05) was validated by RT-qPCR. The MirPath tool was used for MiRNA target prediction and enriched pathways. The top DIANA-mirPath pathways regulated by the targets of the 43 miRNAs are TGF-beta signaling, Proteoglycans in cancer, Pathways in cancer, and Adherens junction (7.30 × 10⁻¹⁰ < p < 1.84 × 10⁻⁸). Selected genes regulating the KEGG pathways, i.e., TP53, MDM2, CDKN1A, CDK6, and CCND1, were analyzed. MiRNAs modulated in AK regulate different pathways involved in tumorigenesis, indicating miRNA regulation as a critical step in keratinocyte cancer. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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13 pages, 3188 KiB

Open AccessArticle

Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

by Riccardo Panella, Cody A. Cotton, Valerie A. Maymi, Sachem Best, Kelsey E. Berry, Samuel Lee, Felipe Batalini, Ioannis S. Vlachos, John G. Clohessy, Sakari Kauppinen and Pier Paolo Pandolfi

Biomedicines 2023, 11(5), 1470; https://doi.org/10.3390/biomedicines11051470 - 18 May 2023

Cited by 2 | Viewed by 2068

Abstract

microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and [...] Read more.

microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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17 pages, 1033 KiB

Open AccessArticle

Dysregulation of Serum MicroRNA after Intracerebral Hemorrhage in Aged Mice

by Dominic Robles, De-Huang Guo, Noah Watson, Diana Asante and Sangeetha Sukumari-Ramesh

Biomedicines 2023, 11(3), 822; https://doi.org/10.3390/biomedicines11030822 - 8 Mar 2023

Cited by 4 | Viewed by 1856

Abstract

Stroke is one of the most common diseases that leads to brain injury and mortality in patients, and intracerebral hemorrhage (ICH) is the most devastating subtype of stroke. Though the prevalence of ICH increases with aging, the effect of aging on the pathophysiology [...] Read more.

Stroke is one of the most common diseases that leads to brain injury and mortality in patients, and intracerebral hemorrhage (ICH) is the most devastating subtype of stroke. Though the prevalence of ICH increases with aging, the effect of aging on the pathophysiology of ICH remains largely understudied. Moreover, there is no effective treatment for ICH. Recent studies have demonstrated the potential of circulating microRNAs as non-invasive diagnostic and prognostic biomarkers in various pathological conditions. While many studies have identified microRNAs that play roles in the pathophysiology of brain injury, few demonstrated their functions and roles after ICH. Given this significant knowledge gap, the present study aims to identify microRNAs that could serve as potential biomarkers of ICH in the elderly. To this end, sham or ICH was induced in aged C57BL/6 mice (18–24 months), and 24 h post-ICH, serum microRNAs were isolated, and expressions were analyzed. We identified 28 significantly dysregulated microRNAs between ICH and sham groups, suggesting their potential to serve as blood biomarkers of acute ICH. Among those microRNAs, based on the current literature, miR-124-3p, miR-137-5p, miR-138-5p, miR-219a-2-3p, miR-135a-5p, miR-541-5p, and miR-770-3p may serve as the most promising blood biomarker candidates of ICH, warranting further investigation. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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17 pages, 2317 KiB

Open AccessArticle

Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

by Mauro Esposito, Nicolò Gualandi, Giovanni Spirito, Federico Ansaloni, Stefano Gustincich and Remo Sanges

Biomedicines 2022, 10(12), 3279; https://doi.org/10.3390/biomedicines10123279 - 17 Dec 2022

Cited by 1 | Viewed by 2061

Abstract

LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, [...] Read more.

LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, they could have been positively selected for beneficial cellular functions. Nonetheless, L1 deregulation can be detrimental to the cell, causing diseases such as cancer. The activity of miRNAs represents a fundamental mechanism for controlling transcript levels in somatic cells. These are a class of small non-coding RNAs that cause degradation or translational inhibition of their target transcripts. Beyond this, competitive endogenous RNAs (ceRNAs), mostly made by circular and non-coding RNAs, have been seen to compete for the binding of the same set of miRNAs targeting protein coding genes. In this study, we have investigated whether autonomously transcribed L1s may act as ceRNAs by analyzing public dataset in-silico. We observed that genes sharing miRNA target sites with L1 have a tendency to be upregulated when L1 are overexpressed, suggesting the possibility that L1 might act as ceRNAs. This finding will help in the interpretation of transcriptomic responses in contexts characterized by the specific activation of transposons. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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12 pages, 1305 KiB

Open AccessArticle

MicroRNA Profiling Shows a Time-Dependent Regulation within the First 2 Months Post-Birth and after Mild Neonatal Hypoxia in the Hippocampus from Mice

by Aisling Leavy, Gary P. Brennan and Eva M. Jimenez-Mateos

Biomedicines 2022, 10(11), 2740; https://doi.org/10.3390/biomedicines10112740 - 28 Oct 2022

Cited by 4 | Viewed by 2101

Abstract

Brain development occurs until adulthood, with time-sensitive processes happening during embryo development, childhood, and puberty. During early life and childhood, dynamic changes in the brain are critical for physiological brain maturation, and these changes are tightly regulated by the expression of specific regulatory [...] Read more.

Brain development occurs until adulthood, with time-sensitive processes happening during embryo development, childhood, and puberty. During early life and childhood, dynamic changes in the brain are critical for physiological brain maturation, and these changes are tightly regulated by the expression of specific regulatory genetic elements. Early life insults, such as hypoxia, can alter the course of brain maturation, resulting in lifelong neurodevelopmental conditions. MicroRNAs are small non-coding RNAs, which regulate and coordinate gene expression. It is estimated that one single microRNA can regulate the expression of hundreds of protein-coding genes.. Uncovering the miRNome and microRNA-regulated transcriptomes may help to understand the patterns of genes regulating brain maturation, and their contribution to neurodevelopmental pathologies following hypoxia at Postnatal day 7. Here, using a PCR-based platform, we analyzed the microRNA profile postnatally in the hippocampus of control mice at postnatal day 8, 14, and 42 and after hypoxia at postnatal day 7, to elucidate the set of microRNAs which may be key for postnatal hippocampus maturation. We observed that microRNAs can be divided in four groups based on their temporal expression. Further after an early life insult, hypoxia at P7, 15 microRNAs showed a misregulation over time, including Let7a. We speculated that the transcriptional regulator c-myc is a contributor to this process. In conclusion, here, we observed that microRNAs are regulated postnatally in the hippocampus and alteration of their expression after hypoxia at birth may be regulated by the transcriptional regulator c-myc. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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18 pages, 804 KiB

Open AccessArticle

Genetic Variations miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G and the Risk of Recurrent Pregnancy Loss in Korean Women

by Hui-Jeong An, Sung-Hwan Cho, Han-Sung Park, Ji-Hyang Kim, Young-Ran Kim, Woo-Sik Lee, Jung-Ryeol Lee, Seong-Soo Joo, Eun-Hee Ahn and Nam-Keun Kim

Biomedicines 2022, 10(10), 2395; https://doi.org/10.3390/biomedicines10102395 - 25 Sep 2022

Cited by 2 | Viewed by 1909

Abstract

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of [...] Read more.

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G was carried out by TaqMan miRNA RT-Real Time polymerase chain reaction (PCR). Four polymorphisms were identified, including miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G. MiR-10a dominant model (AA vs. AT + TT) and miR-499bGG genotypes were associated with increased RPL risk (adjusted odds ratio [AOR] = 1.520, 95% confidence interval [CI] = 1.038–2.227, p = 0.032; AOR = 2.956, 95% CI = 1.168–7.482, p = 0.022, respectively). Additionally, both miR-499 dominant (AA vs. AG + GG) and recessive (AA + AG vs. GG) models were significantly associated with increased RPL risk (AOR = 1.465, 95% CI = 1.062–2.020, p = 0.020; AOR = 2.677, 95% CI = 1.066–6.725, p = 0.036, respectively). We further propose that miR-10aA>T, miR-30cA>G, and miR-499bA>G polymorphisms effects could contribute to RPL and should be considered during RPL patient evaluation. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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29 pages, 4963 KiB

Open AccessArticle

Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice

by Marta Barbosa, Marta Santos, Nídia de Sousa, Sara Duarte-Silva, Ana Rita Vaz, António J. Salgado and Dora Brites

Biomedicines 2022, 10(9), 2120; https://doi.org/10.3390/biomedicines10092120 - 29 Aug 2022

Cited by 6 | Viewed by 4731

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated mSOD1 MN (preconditioned) secretome was incubated in spinal cord organotypic cultures from symptomatic mSOD1 mice, the dysregulated homeostatic balance was circumvented. To decipher the therapeutic potential of such preconditioned secretome, we intrathecally injected it in mSOD1 mice at the early stage of the disease (12-week-old). Preconditioned secretome prevented motor impairment and was effective in counteracting muscle atrophy, glial reactivity/dysfunction, and the neurodegeneration of the symptomatic mSOD1 mice. Deficits in corticospinal function and gait abnormalities were precluded, and the loss of gastrocnemius muscle fiber area was avoided. At the molecular level, the preconditioned secretome enhanced NeuN mRNA/protein expression levels and the PSD-95/TREM2/IL-10/arginase 1/MBP/PLP genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice. It also prevented upregulated GFAP/Cx43/S100B/vimentin and inflammatory-associated miRNAs, specifically miR-146a/miR-155/miR-21, which are displayed by symptomatic animals. Collectively, our study highlights the intrathecal administration of the secretome from anti-miR-124-treated mSOD1 MNs as a therapeutic strategy for halting/delaying disease progression in an ALS mouse model. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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11 pages, 724 KiB

Open AccessArticle

Maternal Body Mass Index Is Associated with Profile Variation in Circulating MicroRNAs at First Trimester of Pregnancy

by Kathrine Thibeault, Cécilia Légaré, Véronique Desgagné, Frédérique White, Andrée-Anne Clément, Michelle S. Scott, Pierre-Étienne Jacques, Renée Guérin, Patrice Perron, Marie-France Hivert and Luigi Bouchard

Biomedicines 2022, 10(7), 1726; https://doi.org/10.3390/biomedicines10071726 - 18 Jul 2022

Cited by 5 | Viewed by 1898

Abstract

Many women enter pregnancy with overweight and obesity, which are associated with complications for both the expectant mother and her child. MicroRNAs (miRNAs) are short non-coding RNAs that regulate many biological processes, including energy metabolism. Our study aimed to identify first trimester plasmatic [...] Read more.

Many women enter pregnancy with overweight and obesity, which are associated with complications for both the expectant mother and her child. MicroRNAs (miRNAs) are short non-coding RNAs that regulate many biological processes, including energy metabolism. Our study aimed to identify first trimester plasmatic miRNAs associated with maternal body mass index (BMI) in early pregnancy. We sequenced a total of 658 plasma samples collected between the 4th and 16th week of pregnancy from two independent prospective birth cohorts (Gen3G and 3D). In each cohort, we assessed associations between early pregnancy maternal BMI and plasmatic miRNAs using DESeq2 R package, adjusting for sequencing run and lane, gestational age, maternal age at the first trimester of pregnancy and parity. A total of 38 miRNAs were associated (FDR q < 0.05) with BMI in the Gen3G cohort and were replicated (direction and magnitude of the fold change) in the 3D cohort, including 22 with a nominal p-value < 0.05. Some of these miRNAs were enriched in fatty acid metabolism-related pathways. We identified first trimester plasmatic miRNAs associated with maternal BMI. These miRNAs potentially regulate fatty acid metabolism-related pathways, supporting the hypothesis of their potential contribution to energy metabolism regulation in early pregnancy. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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9 pages, 1410 KiB

Open AccessArticle

Extraction-Free Absolute Quantification of Circulating miRNAs by Chip-Based Digital PCR

by Yuri D’Alessandra, Vincenza Valerio, Donato Moschetta, Ilaria Massaiu, Michele Bozzi, Maddalena Conte, Valentina Parisi, Michele Ciccarelli, Dario Leosco, Veronika A. Myasoedova and Paolo Poggio

Biomedicines 2022, 10(6), 1354; https://doi.org/10.3390/biomedicines10061354 - 8 Jun 2022

Cited by 5 | Viewed by 2364

Abstract

Circulating microRNAs (miRNA) have been proposed as specific biomarkers for several diseases. Quantitative Real-Time PCR (RT-qPCR) is the gold standard technique currently used to evaluate miRNAs expression from different sources. In the last few years, digital PCR (dPCR) emerged as a complementary and [...] Read more.

Circulating microRNAs (miRNA) have been proposed as specific biomarkers for several diseases. Quantitative Real-Time PCR (RT-qPCR) is the gold standard technique currently used to evaluate miRNAs expression from different sources. In the last few years, digital PCR (dPCR) emerged as a complementary and accurate detection method. When dealing with gene expression, the first and most delicate step is nucleic-acid isolation. However, all currently available protocols for RNA extraction suffer from the variable loss of RNA species due to the chemicals and number of steps involved, from sample lysis to nucleic acid elution. Here, we evaluated a new process for the detection of circulating miRNAs, consisting of sample lysis followed by direct evaluation by dPCR in plasma from healthy donors and in the cardiovascular setting. Our results showed that dPCR is able to detect, with high accuracy, low-copy-number as well as highly expressed miRNAs in human plasma samples without the need for RNA extraction. Moreover, we assessed a known myocardial infarction-related miR-133a in acute myocardial infarct patients vs. healthy subjects. In conclusion, our results show the suitability of the extraction-free quantification of circulating miRNAs as disease markers by direct dPCR. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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17 pages, 1530 KiB

Open AccessArticle

Dietary Improvement during Lactation Normalizes miR-26a, miR-222 and miR-484 Levels in the Mammary Gland, but Not in Milk, of Diet-Induced Obese Rats

by Catalina A. Pomar, Pedro Castillo, Andreu Palou, Mariona Palou and Catalina Picó

Biomedicines 2022, 10(6), 1292; https://doi.org/10.3390/biomedicines10061292 - 31 May 2022

Cited by 4 | Viewed by 1945

Abstract

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control [...] Read more.

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control group), with a Western diet (WD) prior to and during gestation and lactation (WD group), or with WD prior to and during gestation but moved to SD during lactation (Rev group) were followed. The WD group showed higher miR-26a, miR-222 and miR-484 levels than the controls in the MG, but the miRNA profile in Rev animals was not different from those of the controls. The WD group also displayed higher miR-125a levels than the Rev group. Dams of the WD group, but not the Rev group, displayed lower mRNA expression levels of Rb1 (miR-26a’s target) and Elovl6 (miR-125a’s target) than the controls in the MG. The WD group also presented lower expression of Insig1 (miR-26a’s target) and Cxcr4 (miR-222’s target) than the Rev group. However, both WD and Rev animals displayed lower expression of Vegfa (miR-484’s target) than the controls. WD animals also showed greater miR-26a, miR-125a and miR-222 levels in the milk than the controls, but no differences were found between the WD and Rev groups. Thus, implementation of a healthy diet during lactation normalizes the expression levels of specific miRNAs and some target genes in the MG of diet-induced obese dams but not in milk. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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Review

Jump to: Editorial, Research

21 pages, 791 KiB

Open AccessReview

Circulating Biomarkers for Cancer Detection: Could Salivary microRNAs Be an Opportunity for Ovarian Cancer Diagnostics?

by Marzia Robotti, Francesca Scebba and Debora Angeloni

Biomedicines 2023, 11(3), 652; https://doi.org/10.3390/biomedicines11030652 - 21 Feb 2023

Cited by 8 | Viewed by 2753

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs with the crucial regulatory functions of gene expression at post-transcriptional level, detectable in cell and tissue extracts, and body fluids. For their stability in body fluids and accessibility to sampling, circulating miRNAs and changes of their concentration [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNAs with the crucial regulatory functions of gene expression at post-transcriptional level, detectable in cell and tissue extracts, and body fluids. For their stability in body fluids and accessibility to sampling, circulating miRNAs and changes of their concentration may represent suitable disease biomarkers, with diagnostic and prognostic relevance. A solid literature now describes the profiling of circulating miRNA signatures for several tumor types. Among body fluids, saliva accurately reflects systemic pathophysiological conditions, representing a promising diagnostic resource for the future of low-cost screening procedures for systemic diseases, including cancer. Here, we provide a review of literature about miRNAs as potential disease biomarkers with regard to ovarian cancer (OC), with an excursus about liquid biopsies, and saliva in particular. We also report on salivary miRNAs as biomarkers in oncological conditions other than OC, as well as on OC biomarkers other than miRNAs. While the clinical need for an effective tool for OC screening remains unmet, it would be advisable to combine within a single diagnostic platform, the tools for detecting patterns of both protein and miRNA biomarkers to provide the screening robustness that single molecular species separately were not able to provide so far. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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15 pages, 402 KiB

Open AccessReview

Occurrence, Role, and Challenges of MicroRNA in Human Breast Milk: A Scoping Review

by Adrianna Kondracka, Paulina Gil-Kulik, Bartosz Kondracki, Karolina Frąszczak, Anna Oniszczuk, Magda Rybak-Krzyszkowska, Jakub Staniczek, Anna Kwaśniewska and Janusz Kocki

Biomedicines 2023, 11(2), 248; https://doi.org/10.3390/biomedicines11020248 - 18 Jan 2023

Cited by 5 | Viewed by 2252

Abstract

MicroRNAs are non-coding segments of RNA involved in the epigenetic modulation of various biological processes. Their occurrence in biological fluids, such as blood, saliva, tears, and breast milk, has drawn attention to their potential influence on health and disease development. Hundreds of microRNAs [...] Read more.

MicroRNAs are non-coding segments of RNA involved in the epigenetic modulation of various biological processes. Their occurrence in biological fluids, such as blood, saliva, tears, and breast milk, has drawn attention to their potential influence on health and disease development. Hundreds of microRNAs have been isolated from breast milk, yet the evidence on their function remains inconsistent and inconclusive. The rationale for the current scoping review is to map the evidence on the occurrence, characterization techniques, and functional roles of microRNAs in breast milk. The review of the sources of this evidence highlights the need to address methodological challenges to achieve future advances in understanding microRNAs in breast milk, particularly their role in conditions such as neoplasms. Nonetheless, remarkable progress has been made in characterizing the microRNA profiles of human breast milk. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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18 pages, 932 KiB

Open AccessReview

An Update on Circular RNA in Pediatric Cancers

by Angela Galardi, Marta Colletti, Alessandro Palma and Angela Di Giannatale

Biomedicines 2023, 11(1), 36; https://doi.org/10.3390/biomedicines11010036 - 23 Dec 2022

Cited by 4 | Viewed by 1827

Abstract

Circular RNAs (circRNAs) are a class of single-stranded closed noncoding RNA molecules which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, only recently there appeared an increased interest in the understanding of their regulatory importance. Among their [...] Read more.

Circular RNAs (circRNAs) are a class of single-stranded closed noncoding RNA molecules which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, only recently there appeared an increased interest in the understanding of their regulatory importance. Among their most relevant characteristics are high stability, abundance and evolutionary conservation among species. CircRNAs are implicated in several cellular functions, ranging from miRNA and protein sponges to transcriptional modulation and splicing. Additionally, circRNAs’ aberrant expression in pathological conditions is bringing to light their possible use as diagnostic and prognostic biomarkers. Their use as indicator molecules of pathological changes is also supported by their peculiar covalent closed cyclic structure which bestows resistance to RNases. Their regulatory role in cancer pathogenesis and metastasis is supported by studies involving human tumors that have investigated different expression profiles of these molecules. As endogenous competitive RNA, circRNAs can regulate tumor proliferation and invasion and they arouse great consideration as potential therapeutic biomarkers and targets for cancer. In this review, we describe the most recent findings on circRNAs in the most common pediatric solid cancers (such as brain tumors, neuroblastomas, and sarcomas) and in more rare ones (such as Wilms tumors, hepatoblastomas, and retinoblastomas). Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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19 pages, 3079 KiB

Open AccessReview

Non Coding RNAs as Regulators of Wnt/β-Catenin and Hippo Pathways in Arrhythmogenic Cardiomyopathy

by Marina Piquer-Gil, Sofía Domenech-Dauder, Marta Sepúlveda-Gómez, Carla Machí-Camacho, Aitana Braza-Boïls and Esther Zorio

Biomedicines 2022, 10(10), 2619; https://doi.org/10.3390/biomedicines10102619 - 18 Oct 2022

Cited by 10 | Viewed by 2674

Abstract

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy histologically characterized by the replacement of myocardium by fibrofatty infiltration, cardiomyocyte loss, and inflammation. ACM has been defined as a desmosomal disease because most of the mutations causing the disease are located in genes encoding desmosomal [...] Read more.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy histologically characterized by the replacement of myocardium by fibrofatty infiltration, cardiomyocyte loss, and inflammation. ACM has been defined as a desmosomal disease because most of the mutations causing the disease are located in genes encoding desmosomal proteins. Interestingly, the instable structures of these intercellular junctions in this disease are closely related to a perturbed Wnt/β-catenin pathway. Imbalance in the Wnt/β-catenin signaling and also in the crosslinked Hippo pathway leads to the transcription of proadipogenic and profibrotic genes. Aiming to shed light on the mechanisms by which Wnt/β-catenin and Hippo pathways modulate the progression of the pathological ACM phenotype, the study of non-coding RNAs (ncRNAs) has emerged as a potential source of actionable targets. ncRNAs comprise a wide range of RNA species (short, large, linear, circular) which are able to finely tune gene expression and determine the final phenotype. Some share recognition sites, thus referred to as competing endogenous RNAs (ceRNAs), and ensure a coordinating action. Recent cancer research studies regarding the key role of ceRNAs in Wnt/β-catenin and Hippo pathways modulation pave the way to better understanding the molecular mechanisms underlying ACM. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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24 pages, 4039 KiB

Open AccessReview

Epigenetic Features in Uterine Leiomyosarcoma and Endometrial Stromal Sarcomas: An Overview of the Literature

by Bruna Cristine de Almeida, Laura Gonzalez dos Anjos, Andrey Senos Dobroff, Edmund Chada Baracat, Qiwei Yang, Ayman Al-Hendy and Katia Candido Carvalho

Biomedicines 2022, 10(10), 2567; https://doi.org/10.3390/biomedicines10102567 - 13 Oct 2022

Cited by 9 | Viewed by 2891

Abstract

There is a consensus that epigenetic alterations play a key role in cancer initiation and its biology. Studies evaluating the modification in the DNA methylation and chromatin remodeling patterns, as well as gene regulation profile by non-coding RNAs (ncRNAs) have led to the [...] Read more.

There is a consensus that epigenetic alterations play a key role in cancer initiation and its biology. Studies evaluating the modification in the DNA methylation and chromatin remodeling patterns, as well as gene regulation profile by non-coding RNAs (ncRNAs) have led to the development of novel therapeutic approaches to treat several tumor types. Indeed, despite clinical and translational challenges, combinatorial therapies employing agents targeting epigenetic modifications with conventional approaches have shown encouraging results. However, for rare neoplasia such as uterine leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS), treatment options are still limited. LMS has high chromosomal instability and molecular derangements, while ESS can present a specific gene fusion signature. Although they are the most frequent types of “pure” uterine sarcomas, these tumors are difficult to diagnose, have high rates of recurrence, and frequently develop resistance to current treatment options. The challenges involving the management of these tumors arise from the fact that the molecular mechanisms governing their progression have not been entirely elucidated. Hence, to fill this gap and highlight the importance of ongoing and future studies, we have cross-referenced the literature on uterine LMS and ESS and compiled the most relevant epigenetic studies, published between 2009 and 2022. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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19 pages, 2113 KiB

Open AccessReview

Exosomal MicroRNAs as Novel Cell-Free Therapeutics in Tissue Engineering and Regenerative Medicine

by Eric Z. Zeng, Isabelle Chen, Xingchi Chen and Xuegang Yuan

Biomedicines 2022, 10(10), 2485; https://doi.org/10.3390/biomedicines10102485 - 5 Oct 2022

Cited by 10 | Viewed by 2558

Abstract

Extracellular vesicles (EVs) are membrane-bound vesicles (50–1000 nm) that can be secreted by all cell types. Microvesicles and exosomes are the major subsets of EVs that exhibit the cell–cell communications and pathological functions of human tissues, and their therapeutic potentials. To further understand [...] Read more.

Extracellular vesicles (EVs) are membrane-bound vesicles (50–1000 nm) that can be secreted by all cell types. Microvesicles and exosomes are the major subsets of EVs that exhibit the cell–cell communications and pathological functions of human tissues, and their therapeutic potentials. To further understand and engineer EVs for cell-free therapy, current developments in EV biogenesis and secretion pathways are discussed to illustrate the remaining gaps in EV biology. Specifically, microRNAs (miRs), as a major EV cargo that exert promising therapeutic results, are discussed in the context of biological origins, sorting and packing, and preclinical applications in disease progression and treatments. Moreover, advanced detection and engineering strategies for exosomal miRs are also reviewed. This article provides sufficient information and knowledge for the future design of EVs with specific miRs or protein cargos in tissue repair and regeneration. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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17 pages, 1475 KiB

Open AccessReview

The Role of miR-29s in Human Cancers—An Update

by Thuy T. P. Nguyen, Kamrul Hassan Suman, Thong Ba Nguyen, Ha Thi Nguyen and Duy Ngoc Do

Biomedicines 2022, 10(9), 2121; https://doi.org/10.3390/biomedicines10092121 - 29 Aug 2022

Cited by 14 | Viewed by 2491

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that directly bind to the 3’ untranslated region (3’-UTR) of the target mRNAs to inhibit their expression. The miRNA-29s (miR-29s) are suggested to be either tumor suppressors or oncogenic miRNAs that are strongly dysregulated in various types [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNAs that directly bind to the 3’ untranslated region (3’-UTR) of the target mRNAs to inhibit their expression. The miRNA-29s (miR-29s) are suggested to be either tumor suppressors or oncogenic miRNAs that are strongly dysregulated in various types of cancer. Their dysregulation alters the expression of their target genes, thereby exerting influence on different cellular pathways including cell proliferation, apoptosis, migration, and invasion, thereby contributing to carcinogenesis. In the present review, we aimed to provide an overview of the current knowledge on the miR-29s biological network and its functions in cancer, as well as its current and potential applications as a diagnostic and prognostic biomarker and/or a therapeutic target in major types of human cancer. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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27 pages, 2912 KiB

Open AccessReview

Small Nucleolar Derived RNAs as Regulators of Human Cancer

by Alexander Bishop Coley, Jeffrey David DeMeis, Neil Yash Chaudhary and Glen Mark Borchert

Biomedicines 2022, 10(8), 1819; https://doi.org/10.3390/biomedicines10081819 - 28 Jul 2022

Cited by 11 | Viewed by 2679

Abstract

In the past decade, RNA fragments derived from full-length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally [...] Read more.

In the past decade, RNA fragments derived from full-length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions and are able to fill the role of tumor-suppressing or tumor-promoting RNAs in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers. Full article

(This article belongs to the Special Issue microRNAs in Health and Disease)

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