Editorial

2 pages, 173 KiB

Open AccessEditorial

by Hsiuying Wang and Yi-Hau Chen

Biomolecules 2021, 11(12), 1810; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11121810 - 02 Dec 2021

Cited by 1 | Viewed by 1131

MicroRNAs (miRNAs), short non-coding RNAs, are involved in the initiation and progression of many human diseases that also play a key role in immune response and drug metabolism modulation [...] Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

Research

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29 pages, 6677 KiB

Open AccessArticle

Computational Identification and Characterization of New microRNAs in Human Platelets Stored in a Blood Bank

by Jersey Heitor da Silva Maués, Caroline de Fátima Aquino Moreira-Nunes and Rommel Mário Rodriguez Burbano

Biomolecules 2020, 10(8), 1173; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10081173 - 12 Aug 2020

Cited by 4 | Viewed by 2908

Abstract

Platelet concentrate (PC) transfusions are widely used to save the lives of patients who experience acute blood loss. MicroRNAs (miRNAs) comprise a class of molecules with a biological role which is relevant to the understanding of storage lesions in blood banks. We used [...] Read more.

Platelet concentrate (PC) transfusions are widely used to save the lives of patients who experience acute blood loss. MicroRNAs (miRNAs) comprise a class of molecules with a biological role which is relevant to the understanding of storage lesions in blood banks. We used a new approach to identify miRNAs in normal human platelet sRNA-Seq data from the GSE61856 repository. We identified a comprehensive miRNA expression profile, where we detected 20 of these transcripts potentially expressed in PCs stored for seven days, which had their expression levels analyzed with simulations of computational biology. Our results identified a new collection of miRNAs (miR-486-5p, miR-92a-3p, miR-103a-3p, miR-151a-3p, miR-181a-5p, and miR-221-3p) that showed a sensitivity expression pattern due to biological platelet changes during storage, confirmed by additional quantitative real-time polymerase chain reaction (qPCR) validation on 100 PC units from 500 healthy donors. We also identified that these miRNAs could transfer regulatory information on platelets, such as members of the let-7 family, by regulating the YOD1 gene, which is a deubiquitinating enzyme highly expressed in platelet hyperactivity. Our results also showed that the target genes of these miRNAs play important roles in signaling pathways, cell cycle, stress response, platelet activation and cancer. In summary, the miRNAs described in this study, have a promising application in transfusion medicine as potential biomarkers to also measure the quality and viability of the PC during storage in blood banks. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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30 pages, 4611 KiB

Open AccessArticle

Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

by Sarah Atef Fahim, Mahmoud Salah Abdullah, Nancy A. Espinoza-Sánchez, Hebatallah Hassan, Ayman M. Ibrahim, Sarah Hamdy Ahmed, George Shakir, Mohamed A. Badawy, Nadia I. Zakhary, Burkhard Greve, Mohamed El-Shinawi, Martin Götte and Sherif Abdelaziz Ibrahim

Biomolecules 2020, 10(7), 1059; https://doi.org/10.3390/biom10071059 - 16 Jul 2020

Cited by 20 | Viewed by 4004

Abstract

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC [...] Read more.

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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16 pages, 2428 KiB

Open AccessArticle

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

by Patricia M. M. Ozawa, Evelyn Vieira, Débora S. Lemos, Ingrid L. Melo Souza, Silvio M. Zanata, Vânia C. Pankievicz, Thalita R. Tuleski, Emanuel M. Souza, Pryscilla F. Wowk, Cícero de Andrade Urban, Flavia Kuroda, Rubens S. Lima, Rodrigo C. Almeida, Daniela F. Gradia, Iglenir J. Cavalli, Luciane R. Cavalli, Danielle Malheiros and Enilze M. S. F. Ribeiro

Biomolecules 2020, 10(1), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010150 - 16 Jan 2020

Cited by 39 | Viewed by 5243

Abstract

MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum [...] Read more.

MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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11 pages, 1228 KiB

Open AccessArticle

Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

by Saray Duran-Sanchon, Elena Vila-Navarro, Maria Marcuello, Juan José Lozano, Jenifer Muñoz, Joaquín Cubiella, Maria Soledad Diez, Luis Bujanda, Angel Lanas, Rodrigo Jover, Vicent Hernández, Enrique Quintero, Marta Herreros-Villanueva, Ana Carmen Martín, Rosa Pérez-Palacios, Rocio Arroyo, Antoni Castells and Meritxell Gironella

Biomolecules 2020, 10(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010016 - 20 Dec 2019

Cited by 10 | Viewed by 3744

Abstract

Background: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in [...] Read more.

Background: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. Methods: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. Results: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. Conclusion: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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12 pages, 1438 KiB

Open AccessArticle

Gene Expression Profiling of MicroRNAs in HPV-Induced Warts and Normal Skin

by Laith N. AL-Eitan, Mansour A. Alghamdi, Amneh H. Tarkhan and Firas A. Al-Qarqaz

Biomolecules 2019, 9(12), 757; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120757 - 21 Nov 2019

Cited by 9 | Viewed by 3260

Abstract

Infection with the human papillomavirus (HPV) is a common occurrence among the global population, with millions of new cases emerging on an annual basis. Dysregulated microRNA (miRNA) expression is increasingly being identified to play a role in a number of different diseases, especially [...] Read more.

Infection with the human papillomavirus (HPV) is a common occurrence among the global population, with millions of new cases emerging on an annual basis. Dysregulated microRNA (miRNA) expression is increasingly being identified to play a role in a number of different diseases, especially in the context of high-risk HPV infection. The present study investigated the miRNA expression profiles of warts induced by low-risk HPV. In warts, miR-27b, miR-24-1, miR-3654, miR-647, and miR-1914 were downregulated while miR-612 was upregulated compared to normal skin. Using miRTargetLink Human, experimentally supported evidence was obtained showing that miR-27b targeted the vascular endothelial growth factor C (VEGFC) and CAMP-responsive element binding protein 1 (CREB1) genes. The VEGFC and CREB1 genes have been reported to be involved in tumorigenesis and wart formation, respectively. Similarly, the oxidized low-density lipoprotein receptor 1 (OLR1) gene, which plays an important role in the humoral immunity of the skin, and the plexin D1 (PLXND1) gene, which is highly expressed in tumor vasculature, were both found to be common targets of miR-27b, miR-1914, and miR-612. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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Review

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23 pages, 1470 KiB

Open AccessReview

Circulating miRNAs: A New Opportunity in Bone Fragility

by Simone Donati, Simone Ciuffi, Gaia Palmini and Maria Luisa Brandi

Biomolecules 2020, 10(6), 927; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10060927 - 18 Jun 2020

Cited by 16 | Viewed by 2655

Abstract

Osteoporosis, one of the leading causes of bone fractures, is characterized by low bone mass and structural deterioration of bone tissue, which are associated with a consequent increase in bone fragility and predisposition to fracture. Current screening tools are limited in estimating the [...] Read more.

Osteoporosis, one of the leading causes of bone fractures, is characterized by low bone mass and structural deterioration of bone tissue, which are associated with a consequent increase in bone fragility and predisposition to fracture. Current screening tools are limited in estimating the proper assessment of fracture risk, highlighting the need to discover novel more suitable biomarkers. Genetic and environmental factors are both implicated in this disease. Increasing evidence suggests that epigenetics and, in particular, miRNAs, may represent a link between these factors and an increase of fracture risk. miRNAs are a class of small noncoding RNAs that negatively regulate gene expression. In the last decade, several miRNAs have been associated with the development of osteoporosis and bone fracture risk, opening up new possibilities in precision medicine. Recently, these molecules have been identified in several biological fluids, and the possible existence of a circulating miRNA (c-miRNA) signature years before the fracture occurrence is suggested. The aim of this review is to provide an overview of the c-miRNAs suggested as promising biomarkers for osteoporosis up until now, which could be helpful for early diagnosis and monitoring of treatment response, as well as fracture risk assessment, in osteoporotic patients. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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29 pages, 363 KiB

Open AccessReview

The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases

by Michela Bottani, Giuseppe Banfi and Giovanni Lombardi

Biomolecules 2020, 10(4), 589; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040589 - 11 Apr 2020

Cited by 39 | Viewed by 3421

Abstract

Osteoporosis, related fracture/fragility, and osteoarthritis are age-related pathologies that, over recent years, have seen increasing incidence and prevalence due to population ageing. The diagnostic approaches to these pathologies suffer from limited sensitivity and specificity, also in monitoring the disease progression or treatment. For [...] Read more.

Osteoporosis, related fracture/fragility, and osteoarthritis are age-related pathologies that, over recent years, have seen increasing incidence and prevalence due to population ageing. The diagnostic approaches to these pathologies suffer from limited sensitivity and specificity, also in monitoring the disease progression or treatment. For this reason, new biomarkers are desirable for improving the management of osteoporosis and osteoarthritis patients. The non-coding RNAs, called miRNAs, are key post-transcriptional factors in bone homeostasis, and promising circulating biomarkers for pathological conditions in which to perform a biopsy can be problematic. In fact, miRNAs can easily be detected in biological fluids (i.e., blood, serum, plasma) using methods with elevated sensitivity and specificity (RT-qPCR, microarray, and NGS). However, the analytical phases required for miRNAs’ evaluation still present some practical issues that limit their use in clinical practice. This review reveals miRNAs’ potential as circulating biomarkers for evaluating predisposition, diagnosis, and prognosis of osteoporosis (postmenopausal or idiopathic), bone fracture/fragility, and osteoarthritis, with a focus on pre-analytical, analytical, and post-analytical protocols used for their validation and thus on their clinical applicability. These evidences may support the definition of early diagnostic tools based on circulating miRNAs for bone diseases and osteoarthritis as well as for monitoring the effects of specific treatments. Full article

(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)

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