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Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: "Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?" Methods: The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health "Study Quality Assessment Tool" and the classification of the Oxford Center for Evidence-Based Medicine. Results: Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having "good" quality, the rest being scored as "intermediate" (8; 73%) and "poor" (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer. Conclusions: Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers. [ABSTRACT FROM AUTHOR]

There is an unmet need for novel non-invasive prognostic molecular tumour markers for breast cancer (BC). Accumulating evidence shows that miR-155 plays a pivotal role in tumorigenesis. Generally, miR-155 is considered an oncogenic miRNA promoting tumour growth, angiogenesis and aggressiveness of BC. Therefore, many researchers have focused on its use as a prognostic biomarker and therapeutic target. However, its prognostic value for BC patients remains controversial. To address this issue, the present systematic review aims to summarize the available evidence and give a picture of a prognostic significance of miR-155 in BC pathology. All eligible studies were searched on PubMed and EMBASE databases through various search strategies. Starting from 289 potential eligible records, data were examined from 28 studies, comparing tissue and circulating miR-155 expression levels with clinicopathological features and survival rates in BC patients. We discuss the pitfalls and challenges that need to be assessed to understand the power of miR-155 to respond to real clinical needs, highlighting the consistency, robustness or lack of results obtained to sate in translating this molecule to clinical practice. Our paper suggests that the prognostic role of miR-155 in the management of BC needs to be further verified. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of morbidity and mortality in Western societies. Statins are the first-choice therapy for dislipidemias and are considered the cornerstone of ASCVD. Statin-associated muscle symptoms are the main reason for dropout of this treatment. There is an urgent need to identify new biomarkers with discriminative precision for diagnosing intolerance to statins (SI) in patients. MicroRNAs (miRNAs) have emerged as evolutionarily conserved molecules that serve as reliable biomarkers and regulators of multiple cellular events in cardiovascular diseases. In the current study, we evaluated plasma miRNAs as potential biomarkers to discriminate between the SI vs. non-statin intolerant (NSI) population. It is a multicenter, prospective, case-control study. A total of 179 differentially expressed circulating miRNAs were screened in two cardiovascular risk patient cohorts (high and very high risk): (i) NSI (n = 10); (ii) SI (n = 10). Ten miRNAs were identified as being overexpressed in plasma and validated in the plasma of NSI (n = 45) and SI (n = 39). Let-7c-5p, let-7d-5p, let-7f-5p, miR-376a-3p and miR-376c-3p were overexpressed in the plasma of SI patients. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. We propose a three-miRNA predictive fingerprint (let-7f, miR-376a-3p and miR-376c-3p) and several clinical variables (non-HDLc and years of dyslipidemia) for SI discrimination; this model achieves sensitivity, specificity and area under the receiver operating characteristic curve (AUC) of 83.67%, 88.57 and 89.10, respectively. In clinical practice, this set of miRNAs combined with clinical variables may discriminate between SI vs. NSI subjects. This multiparametric model may arise as a potential diagnostic biomarker with clinical value. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. [ABSTRACT FROM AUTHOR]

Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients' response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5-10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs' stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy. [ABSTRACT FROM AUTHOR]