The Eminent Role of microRNAs in the Pathogenesis of Alzheimer's Disease

Alzheimer's disease (AD) is an irrevocable neurodegenerative condition characterized by the presence of senile plaques comprising amassed β-amyloid peptides (Aβ) and neurofibrillary tangles mainly comprising extremely phosphorylated Tau proteins. Recent studies have emphasized the role of microRNAs (miRNAs) in the development of AD. A number of miRNAs, namely, miR-200a-3p, miR-195, miR-338-5p, miR-34a-5p, miR-125b-5p, miR-132, miR-384, miR-339-5p, miR-135b, miR-425-5p, and miR-339-5p, have been shown to participate in the development of AD through interacting with BACE1. Other miRNAs might affect the inflammatory responses in the course of AD. Aberrant expression of several miRNAs in the plasma samples of AD subjects has been shown to have the aptitude for differentiation of AD subjects from healthy subjects. Finally, a number of AD-modifying agents affect miRNA profile in cell cultures or animal models. We have performed a comprehensive search and summarized the obtained data about the function of miRNAs in AD in the current review article. © Copyright © 2021 Samadian, Gholipour, Hajiesmaeili, Taheri and Ghafouri-Fard

The emerging role of non-coding RNAs in the regulation of PI3K/AKT pathway in the carcinogenesis process

The PI3K/AKT pathway is an intracellular signaling pathway with an indispensable impact on cell cycle control. This pathway is functionally related with cell proliferation, cell survival, metabolism, and quiescence. The crucial role of this pathway in the development of cancer has offered this pathway as a target of novel anti-cancer treatments. Recent researches have demonstrated the role of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in controlling the PI3K/AKT pathway. Some miRNAs such as miR-155-5p, miR-328-3p, miR-125b-5p, miR-126, miR-331-3p and miR-16 inactivate this pathway, while miR-182, miR-106a, miR-193, miR-214, miR-106b, miR-93, miR-21 and miR-103/107 enhance activity of this pathway. Expression levels of PI3K/AKT-associated miRNAs could be used to envisage the survival of cancer patients. Numerous lncRNAs such as GAS5, FER1L4, LINC00628, PICART1, LOC101928316, ADAMTS9-AS2, SLC25A5-AS1, MEG3, AB073614 and SNHG6 interplay with this pathway. Identification of the impact of miRNAs and lncRNAs in the control of the activity of PI3K/AKT pathway would enhance the efficacy of targeted therapies against this pathway. Moreover, each of the mentioned miRNAs and lncRNAs could be used as a putative therapeutic candidate for the interfering with the carcinogenesis. In the current study, we review the role of miRNAs and lncRNAs in controlling the PI3K/AKT pathway and their contribution to carcinogenesis. © 2021 The Author(s

MIR-206 target prediction in breast cancer subtypes by bioinformatics tools

Background: MicroRNAs (miRNAs) are small endogenous non-coding RNAs with fundamental roles in the regulation of protein expression that is involved in the pathogenesis of many cancers including breast cancer. Among them is miR-206, whose role as a tumor suppressor gene has been demonstrated in breast cancer. Consequently, the identification of its putative target in breast cancer is of practical value. Methods: In the present study, we have suggested a new approach for the identification of miR-206 target genes with possible role in breast cancer pathogenesis. We used 15 online tools for the prediction of miR-206 target genes as well as gene expression data produced by DNA microarray technology. Results: By combining these two sets of data, we suggested a list of miR-206 target genes with possible involvement in breast cancer. In addition, we depicted an interaction network including miR-206 and its putative targets. Conclusions: Considering the complexity of miR-206 interactions with several targets, such in silico analyses would considerably lessen the work load of laboratory experiments. © 2018, Author(s)

miR-1: A comprehensive review of its role in normal development and diverse disorders

MicroRNA-1 (miR-1) is a conserved miRNA with high expression in the muscle tissues. In humans, two discrete genes, MIRN1-1 and MIRN1-2 residing on a genomic region on 18q11.2 produce a single mature miRNA which has 21 nucleotides. miR-1 has a regulatory role on a number of genes including heat shock protein 60 (HSP60), Kruppel-like factor 4 (KLF4) and Heart And Neural Crest Derivatives Expressed 2 (HAND2). miR-1 has critical roles in the physiological processes in the smooth and skeletal muscles as well as other tissues, thus being involved in the pathogenesis of a wide range of disorders. Moreover, dysregulation of miR-1 has been noted in diverse types of cancers including gastric, colorectal, breast, prostate and lung cancer. In the current review, we provide the summary of the data regarding the role of this miRNA in the normal development and the pathogenic processes. © 2020 The Author(s

Non-coding RNAs modulate function of extracellular matrix proteins

The extracellular matrix (ECM) creates a multifaceted system for the interaction of diverse structural proteins, matricellular molecules, proteoglycans, hyaluronan, and various glycoproteins that collaborate and bind with each other to produce a bioactive polymer. Alterations in the composition and configuration of ECM elements influence the cellular phenotype, thus participating in the pathogenesis of several human disorders. Recent studies indicate the crucial roles of non-coding RNAs in the modulation of ECM. Several miRNAs such as miR-21, miR-26, miR-19, miR-140, miR-29, miR-30, miR-133 have been dysregulated in disorders that are associated with disruption or breakdown of the ECM. Moreover, expression of MALAT1, PVT1, SRA1, n379519, RMRP, PFL, TUG1, TM1P3, FAS-AS1, PART1, XIST, and expression of other lncRNAs is altered in disorders associated with the modification of ECM components. In the current review, we discuss the role of lncRNAs and miRNAs in the modification of ECM and their relevance with the pathophysiology of human disorders such as cardiac/ lung fibrosis, cardiomyopathy, heart failure, asthma, osteoarthritis, and cancers. © 2021 The Author(s

Machine learning for genetic prediction of psychiatric disorders: a systematic review

Machine learning methods have been employed to make predictions in psychiatry from genotypes, with the potential to bring improved prediction of outcomes in psychiatric genetics; however, their current performance is unclear. We aim to systematically review machine learning methods for predicting psychiatric disorders from genetics alone and evaluate their discrimination, bias and implementation. Medline, PsycInfo, Web of Science and Scopus were searched for terms relating to genetics, psychiatric disorders and machine learning, including neural networks, random forests, support vector machines and boosting, on 10 September 2019. Following PRISMA guidelines, articles were screened for inclusion independently by two authors, extracted, and assessed for risk of bias. Overall, 63 full texts were assessed from a pool of 652 abstracts. Data were extracted for 77 models of schizophrenia, bipolar, autism or anorexia across 13 studies. Performance of machine learning methods was highly varied (0.48–0.95 AUC) and differed between schizophrenia (0.54–0.95 AUC), bipolar (0.48–0.65 AUC), autism (0.52–0.81 AUC) and anorexia (0.62–0.69 AUC). This is likely due to the high risk of bias identified in the study designs and analysis for reported results. Choices for predictor selection, hyperparameter search and validation methodology, and viewing of the test set during training were common causes of high risk of bias in analysis. Key steps in model development and validation were frequently not performed or unreported. Comparison of discrimination across studies was constrained by heterogeneity of predictors, outcome and measurement, in addition to sample overlap within and across studies. Given widespread high risk of bias and the small number of studies identified, it is important to ensure established analysis methods are adopted. We emphasise best practices in methodology and reporting for improving future studies

Emerging role of circular RNAs in breast cancer

Circular RNAs (cirRNAs) are generally considered as non-coding RNAs which can act as molecular sponges for miRNAs, exert regulatory roles in transcription or splicing, and interplay with RNA binding proteins. These single-stranded transcripts can affect tumor growth, the metastatic ability of cancer cells, stemness properties, and resistance to therapeutic options. Recent investigations have shown the crucial effects of circrNAs in the evolution of breast cancer. Signature of circRNAs in breast cancer samples has been mostly assessed through microarray-based methods revealing up-regulation of some circRNAs such as circ-TFF1, circACAP2, circ-TFCP2L1, hsacirc0000519, circDENND4C, circPLK1 and circRNA069718, while down-regulation of other circRNAs such as hsacirc0000375, circYap, hsacirc0025202, circTADA2A-E6, circASS1 and circRNABARD1 in breast cancer samples. Mechanistically, these transcripts mainly affect breast cancer tumorigenesis via serving as sponges for miRNAs. In the current manuscript, we explore the results of researches that appraised the role of circRNAs in breast cancer. © 2021 Elsevier Gmb