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Biology of Reproduction Mar 2023The molecular mechanism of non-tumor female reproductive diseases is complicated and needs to be further elucidated. Recently, increasing evidence indicates that... (Review)
Review
The molecular mechanism of non-tumor female reproductive diseases is complicated and needs to be further elucidated. Recently, increasing evidence indicates that non-coding RNAs(ncRNAs) which are extremely rich in the female reproductive system are crucial factors in the pathogenesis of some female reproductive disorders. In fact, these ncRNAs such as lncRNAs, circRNAs, snoRNAs, and pseudogenes that share the same miRNA response elements (MREs) with mRNAs could compete for miRNA binding site to regulate gene expression, this phenomenon is known as the competing endogenous RNAs(ceRNAs) mechanism. This review aims to summarize the role of ceRNAs in cell proliferation, apoptosis, migration, and invasion of non-tumor female reproductive diseases such as polycystic ovary syndrome (PCOS), premature ovarian failure (POF), pre-eclampsia (PE), recurrent implantation failure (RIF), recurrent spontaneous abortion (RSA), endometriosis (EM), and endometritis, and list ceRNAs regulatory axes as well as downstream related signaling pathway. Additionally, based on certain ncRNAs that have already been proven to exist at differential levels in patient tissue samples, we also generalize some ncRNAs that can be used as potential biomarkers and therapeutic targets for these diseases in the future.
Topics: Humans; Female; Gene Regulatory Networks; MicroRNAs; RNA, Messenger; RNA, Circular; RNA, Long Noncoding
PubMed: 36355359
DOI: 10.1093/biolre/ioac200 -
Epigenomics Mar 2020Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant... (Review)
Review
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
Topics: Biomarkers, Tumor; Humans; Male; MicroRNAs; Prostatic Neoplasms
PubMed: 32267174
DOI: 10.2217/epi-2019-0275 -
Journal of Clinical Laboratory Analysis Feb 2020MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical...
BACKGROUND
MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical application is low.
METHODS
Detection of plasma miRNAs was optimized by analyzing factors influencing miRNA variance and myocardial infarction risk scores during analysis (extraction, reverse transcription, and real-time PCR) and pre-analysis (dietary status, anticoagulants, storage conditions, and hemolysis).
RESULTS
Regarding variable factors during analysis, the centrifugal column method was superior to Trizol LS reagent when extracting miRNA from plasma. Recovery rate was highest with plasma volumes of 200 and 300 µL. During analysis, the main source of miRNA detection inaccuracy was derived from RNA extraction (mainly organic extraction), and not reverse transcription or PCR. MiRNA variance could be reduced by use of an internal reference. During analysis, 95% of risk score variation fluctuated within a range of 6.267. The variable factors pre-analysis mainly involved dietary status, anticoagulant selection, and storage conditions. Hemolysis positively correlated with miRNA levels, but there was no significant change in risk score after internal reference calibration.
CONCLUSION
Preliminary standardization for miRNA detection provides a reference for clinical blood testing of miRNAs.
Topics: Adult; Aged; Anticoagulants; Blood Specimen Collection; Fasting; Female; Hemolysis; Humans; Male; MicroRNAs; Middle Aged; Myocardial Infarction; Real-Time Polymerase Chain Reaction; Reproducibility of Results
PubMed: 31617231
DOI: 10.1002/jcla.23058 -
Acta Neuropathologica Jun 2021Pituitary blastoma (PitB) has recently been identified as a rare and potentially lethal pediatric intracranial tumor. All cases that have been studied molecularly...
Pituitary blastoma (PitB) has recently been identified as a rare and potentially lethal pediatric intracranial tumor. All cases that have been studied molecularly possess at least one DICER1 pathogenic variant. Here, we characterized nine pituitary samples, including three fresh frozen PitBs, three normal fetal pituitary glands and three normal postnatal pituitary glands using small-RNA-Seq, RNA-Seq, methylation profiling, whole genome sequencing and Nanostring® miRNA analyses; an extended series of 21 pituitary samples was used for validation purposes. These analyses demonstrated that DICER1 RNase IIIb hotspot mutations in PitBs induced improper processing of miRNA precursors, resulting in aberrant 5p-derived miRNA products and a skewed distribution of miRNAs favoring mature 3p over 5p miRNAs. This led to dysregulation of hundreds of 5p and 3p miRNAs and concomitant dysregulation of numerous mRNA targets. Gene expression analysis revealed PRAME as the most significantly upregulated gene (500-fold increase). PRAME is a member of the Retinoic Acid Receptor (RAR) signaling pathway and in PitBs, the RAR, WNT and NOTCH pathways are dysregulated. Cancer Hallmarks analysis showed that PI3K pathway is activated in the tumors. Whole genome sequencing demonstrated a quiet genome with very few somatic alterations. The comparison of methylation profiles to publicly available data from ~ 3000 other central nervous system tumors revealed that PitBs have a distinct methylation profile compared to all other tumors, including pituitary adenomas. In conclusion, this comprehensive characterization of DICER1-related PitB revealed key molecular underpinnings of PitB and identified pathways that could potentially be exploited in the treatment of this tumor.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Child; Child, Preschool; DEAD-box RNA Helicases; Enhancer of Zeste Homolog 2 Protein; Female; Fetus; Humans; Ki-67 Antigen; Male; Methylation; MicroRNAs; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases; Pituitary Neoplasms; Ribonuclease III; Sequence Analysis, RNA; Signal Transduction; Tissue Array Analysis; Whole Genome Sequencing
PubMed: 33644822
DOI: 10.1007/s00401-021-02283-6 -
Wiley Interdisciplinary Reviews. RNA Jan 2023MicroRNA (miRNA) is regarded as a prominent genetic regulator, as it can fine-tune an entire biological pathway by targeting multiple target genes. This characteristic... (Review)
Review
MicroRNA (miRNA) is regarded as a prominent genetic regulator, as it can fine-tune an entire biological pathway by targeting multiple target genes. This characteristic makes miRNAs promising therapeutic tools to reinstate cell functions that are disrupted as a consequence of diseases. Currently, miRNA replacement by miRNA mimics and miRNA inhibition by anti-miRNA oligonucleotides are the main approaches to utilizing miRNA molecules for therapeutic purposes. Nevertheless, miRNA-based therapeutics are hampered by major issues such as off-target effects, immunogenicity, and uncertain delivery platforms. Over the past few decades, several innovative approaches have been established to minimize off-target effects, reduce immunostimulation, and provide efficient transfer to the target cells in which these molecules exert their function. Recent achievements have led to the testing of miRNA-based drugs in clinical trials, and these molecules may become next-generation therapeutics for medical intervention. Despite the achievement of exciting milestones, the dosage of miRNA administration remains unclear, and ways to address this issue are proposed. Elucidating the current status of the main factors of therapeutic miRNA would allow further developments and innovations to achieve safe therapeutic tools. This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.
Topics: MicroRNAs
PubMed: 36437633
DOI: 10.1002/wrna.1768 -
International Journal of Molecular... Dec 2022Mature microRNAs (miRNAs) are single-stranded non-coding RNA (ncRNA) molecules that act in post-transcriptional regulation in animals and plants. A mature miRNA is the... (Review)
Review
Mature microRNAs (miRNAs) are single-stranded non-coding RNA (ncRNA) molecules that act in post-transcriptional regulation in animals and plants. A mature miRNA is the end product of consecutive, highly regulated processing steps of the primary miRNA transcript. Following base-paring of the mature miRNA with its mRNA target, translation is inhibited, and the targeted mRNA is degraded. There are hundreds of miRNAs in each cell that work together to regulate cellular key processes, including development, differentiation, cell cycle, apoptosis, inflammation, viral infection, and more. In this review, we present an overlooked layer of cellular regulation that addresses cell dynamics affecting miRNA accessibility. We discuss the regulation of miRNA local storage and translocation among cell compartments. The local amounts of the miRNAs and their targets dictate their actual availability, which determines the ability to fine-tune cell responses to abrupt or chronic changes. We emphasize that changes in miRNA storage and compactization occur under induced stress and changing conditions. Furthermore, we demonstrate shared principles on cell physiology, governed by miRNA under oxidative stress, tumorigenesis, viral infection, or synaptic plasticity. The evidence presented in this review article highlights the importance of spatial and temporal miRNA regulation for cell physiology. We argue that limiting the research to mature miRNAs within the cytosol undermines our understanding of the efficacy of miRNAs to regulate cell fate under stress conditions.
Topics: Animals; MicroRNAs; Gene Expression Regulation; RNA, Messenger; Cell Differentiation; Homeostasis
PubMed: 36555797
DOI: 10.3390/ijms232416152 -
Methods in Molecular Biology (Clifton,... 2021Research on RNA function and therapeutic potential is dominated by the use of chemoengineered RNA mimics. Recent efforts have led to the establishment of novel...
Research on RNA function and therapeutic potential is dominated by the use of chemoengineered RNA mimics. Recent efforts have led to the establishment of novel technologies for the production of recombinant or bioengineered RNA molecules, which should better recapitulate the structures, functions and safety profiles of natural RNAs because both are produced and folded in living cells. Herein, we describe a robust approach for reproducible fermentation production of bioengineered RNA agents (BERAs) carrying warhead miRNAs, siRNAs, aptamers, or other forms of small RNAs, based upon an optimal hybrid tRNA/pre-miRNA carrier. Target BERA/sRNAs are readily purified by fast protein liquid chromatography (FPLC) to a high degree of homogeneity (>97%). This approach offers a consistent high-level expression (>30% of total bacterial RNAs) and large-scale production of ready-to-use BERAs (multiple to tens milligrams from 1 L bacterial culture).
Topics: Base Sequence; Bioengineering; Chromatography, Ion Exchange; Cloning, Molecular; Drug Contamination; Electrophoresis, Polyacrylamide Gel; Endotoxins; Escherichia coli; Fermentation; MicroRNAs; Nucleic Acid Denaturation; Plasmids; Polymerase Chain Reaction; RNA; RNA, Bacterial; RNA, Transfer; RNA, Untranslated
PubMed: 34086286
DOI: 10.1007/978-1-0716-1499-0_18 -
Life Sciences Aug 2022Ischemia-reperfusion (I/R) injury is a leading cause of death worldwide. It arises from blood reflowing after tissue hypoxia induced by ischemia that causes severe... (Review)
Review
Ischemia-reperfusion (I/R) injury is a leading cause of death worldwide. It arises from blood reflowing after tissue hypoxia induced by ischemia that causes severe damages due to the accumulation of reactive oxygen species and the activation of inflammatory responses. Exosomes are the smallest members of the extracellular vesicles' family, which originate from nearly all eukaryotic cells. Exosomes have a great potential in the treatment of I/R injury either in native or modified forms. Native exosomes are secreted by different cell types, such as stem cells, and contain components such as specific miRNA molecules with tissue protective properties. On the other hand, exosome bioengineering has recently received increased attention in context of current advances in the purification, manipulation, biological characterization, and pharmacological applications. There are various pre-isolation and post-isolation manipulation approaches that can be utilized to increase the circulation half-life of exosomes or the availability of their bioactive cargos in the target site. In this review, the various therapeutic actions of native exosomes in different I/R injury will be discussed first. Exosome bioengineering approaches will then be explained, including pre- and post-isolation manipulation methods, applicability for delivery of bioactive agents to injured tissue, clinical translation issues, and future perspectives.
Topics: Humans; Exosomes; Reperfusion Injury; MicroRNAs; Bioengineering; Ischemia
PubMed: 35597547
DOI: 10.1016/j.lfs.2022.120654 -
Minerva Obstetrics and Gynecology Feb 2024MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that play a role in regulating gene expression in a tissue-specific manner. Placental miRNAs... (Review)
Review
MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that play a role in regulating gene expression in a tissue-specific manner. Placental miRNAs expression pattern dynamically changes during pregnancy influencing cell proliferation, differentiation and apoptosis. Changes of specific miRNA levels have been described in pregnancies complicated by hypertensive disorders or gestational diabetes and a growing interest in understanding miRNA role on placental development and placental disorders is currently going on. The present review evaluates the possible roles of miRNAs in trophoblastic invasion and placental development as well as their potential role as biomarkers for the prediction of placental disorders focusing the attention on intrauterine growth restriction.
Topics: Pregnancy; Humans; Female; MicroRNAs; Pre-Eclampsia; Placenta; Fetal Growth Retardation; Trophoblasts; Placenta Diseases
PubMed: 36222784
DOI: 10.23736/S2724-606X.22.05109-0 -
Biomolecules Sep 2020Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide... (Review)
Review
Coronary artery disease (CAD) is the leading cause of sudden cardiac death in adults, and new methods of predicting disease and risk-stratifying patients will help guide intervention in order to reduce this burden. Current CAD detection involves multiple modalities, but the consideration of other biomarkers will help improve reliability. The aim of this narrative review is to help researchers and clinicians appreciate the growing relevance of miRNA in CAD and its potential as a biomarker, and also to suggest useful miRNA that may be targets for future study. We sourced information from several databases, namely PubMed, Scopus, and Google Scholar, when collating evidentiary information. MicroRNAs (miRNA) are short, noncoding RNAs that are relevant in cardiovascular physiology and pathophysiology, playing roles in cardiac hypertrophy, maintenance of vascular tone, and responses to vascular injury. CAD is associated with changes in miRNA expression profiles, and so are its risk factors, such as abnormal lipid metabolism and inflammation. Thus, they may potentially be biomarkers of CAD. Nevertheless, there are limitations in using miRNA. These include cost and the presence of several confounding factors that may affect miRNA profiles. Furthermore, there is difficulty in the normalisation of miRNA values between published studies, due to pre-analytical variations in samples.
Topics: Biomarkers; Circulating MicroRNA; Coronary Artery Disease; Humans; MicroRNAs; Risk Factors
PubMed: 32977454
DOI: 10.3390/biom10101354