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International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
Pathology, Research and Practice Sep 2023Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as... (Review)
Review
Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome's q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.
Topics: Humans; Neoplasms; MicroRNAs; Apoptosis; RNA, Messenger
PubMed: 37660658
DOI: 10.1016/j.prp.2023.154770 -
Circulation. Arrhythmia and... Jan 2024MicroRNA-1 (miR1), encoded by the genes and , is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of...
BACKGROUND
MicroRNA-1 (miR1), encoded by the genes and , is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling.
METHODS
or knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; or ) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays.
RESULTS
In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na current and transient outward potassium current, coupled with elevated L-type Ca current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1's RNA interference-direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias.
CONCLUSIONS
miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.
Topics: Mice; Humans; Animals; MicroRNAs; Proteomics; Ventricular Remodeling; Myocytes, Cardiac; Arrhythmias, Cardiac; Action Potentials; Mice, Knockout; Homeostasis
PubMed: 38126205
DOI: 10.1161/CIRCEP.123.012150 -
European Journal of Pharmacology Oct 2023MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression.... (Review)
Review
MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.
Topics: Humans; MicroRNAs; Neoplasms; RNA Interference; Treatment Outcome; Brain Injuries, Traumatic; Central Nervous System Diseases
PubMed: 37541374
DOI: 10.1016/j.ejphar.2023.175956 -
Medical Oncology (Northwood, London,... Jul 2023Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and it poses a significant risk to patients health and longevity due to its high... (Review)
Review
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and it poses a significant risk to patients health and longevity due to its high morbidity and fatality rates. Surgical ablation, radiotherapy, chemotherapy, and, most recently, immunotherapy have all been investigated for HCC, but none have yielded the desired outcomes. Several unique nanocarrier drug delivery techniques have been studied for their potential therapeutic implications in the treatment of HCC. Nanoparticle-based imaging could be effective for more accurate HCC diagnosis. Since its inception, nanomedicine has significantly transformed the approach to both the treatment and diagnostics of liver cancer. Nanoparticles (NPs) are being studied as a potential treatment for liver cancer because of their ability to carry small substances, such as treatment with chemotherapy, microRNA, and therapeutic genes. The primary focus of this study is on the most current discoveries and practical uses of nanomedicine-based diagnostic and therapeutic techniques for liver cancer. In this section, we had gone over what we know about metabolic dysfunction in HCC and the treatment options that attempt to fix it by targeting metabolic pathways. Furthermore, we propose a multi-target metabolic strategy as a viable HCC treatment option. Based on the findings given here, the scientists believe that smart nanomaterials have great promise for improving cancer theranostics and opening up new avenues for tumor diagnosis and treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Drug Delivery Systems; MicroRNAs; Immunotherapy; Nanoparticles
PubMed: 37442842
DOI: 10.1007/s12032-023-02104-8 -
Experimental Eye Research Jun 2024Myopia, the most prevalent eye condition, has sparked notable interest regarding its origin and prevention. MicroRNAs (miRNAs) are short, non-coding RNA strands... (Review)
Review
Myopia, the most prevalent eye condition, has sparked notable interest regarding its origin and prevention. MicroRNAs (miRNAs) are short, non-coding RNA strands typically consisting of 18-24 nucleotides. They play a central role in post-transcriptional gene regulation and are closely associated with both normal and pathological processes in organisms. Recent advances in next-generation sequencing and bioinformatics have provided novel insights into miRNA expression and its regulatory role in myopia. This review discusses the distinct expression patterns, regulatory functions, and potential pathways of miRNAs involved in the onset and progression of myopia. The primary objective of this review was to provide valuable insights into molecular mechanisms underlying myopia and the contribution of miRNAs. These insights are expected to pave the way for further exploration of the molecular mechanisms, diagnosis, treatment, and clinical applications of myopia.
Topics: Humans; MicroRNAs; Myopia; Gene Expression Regulation
PubMed: 38642599
DOI: 10.1016/j.exer.2024.109905 -
Journal of Molecular Histology Dec 2023Therapeutic and diagnostic progresses have significantly reduced the mortality rate among cancer patients during the last decade. However, there is still a high rate of... (Review)
Review
Therapeutic and diagnostic progresses have significantly reduced the mortality rate among cancer patients during the last decade. However, there is still a high rate of mortality among cancer patients. One of the important reasons involved in the high mortality rate is the late diagnosis in advanced tumor stages that causes the failure of therapeutic strategies in these patients. Therefore, investigating the molecular mechanisms involved in tumor progression has an important role in introducing the efficient early detection markers. MicroRNAs (miRNAs) as stable factors in body fluids are always considered as non-invasive diagnostic and prognostic markers. In the present review, we investigated the role of miR-495 in tumor progression. It has been reported that miR-495 has mainly a tumor suppressor function through the regulation of transcription factors and tyrosine kinases as well as cellular processes such as multidrug resistance, chromatin remodeling, and signaling pathways. This review can be an effective step towards introducing the miR-495 as a non-invasive diagnostic/prognostic marker as well as a suitable target in tumor therapy.
Topics: Humans; Biomarkers, Tumor; Neoplasms; MicroRNAs; Prognosis; Signal Transduction; Gene Expression Regulation, Neoplastic
PubMed: 37759132
DOI: 10.1007/s10735-023-10159-0 -
Journal of Physiology and Biochemistry May 2024In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn... (Review)
Review
In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn control many important physiological processes, such as cell proliferation, distinctions, invasion, angiogenesis, and embryonic development. microRNA-126 is an important member of these miRNAs that can be directly or indirectly involved in the control of angiogenesis. Recently, numerous studies have expounded that microRNA-126 can inhibit or promote angiogenesis as well as attenuate inflammatory responses through complex molecular mechanisms. As such, it serves as a biomarker or potential therapeutic target for the prediction, diagnosis, and treatment of relevant diseases. In this review, we present the advancements in research regarding microRNA-126's role in the diagnosis and treatment of related diseases, aiming to provide innovative therapeutic options for the diagnosis and treatment of clinically relevant diseases.
Topics: MicroRNAs; Humans; Animals; Neovascularization, Pathologic; Neoplasms
PubMed: 38517589
DOI: 10.1007/s13105-024-01017-y -
World Journal of Gastroenterology Oct 2023Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to... (Review)
Review
Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO) buffer system "biliary HCO umbrella". The impaired production and entry of HCO from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.
Topics: Humans; Liver Cirrhosis, Biliary; Bile Ducts; Epithelial Cells; Cholestasis; Bile Acids and Salts; Cholangitis; MicroRNAs
PubMed: 37899787
DOI: 10.3748/wjg.v29.i37.5292 -
Progress in Molecular Biology and... 2024The study of small RNAs is a field that is expanding quickly. Other functional short RNA molecules other than microRNAs, and gene expression regulators, have been found... (Review)
Review
The study of small RNAs is a field that is expanding quickly. Other functional short RNA molecules other than microRNAs, and gene expression regulators, have been found in animals and plants. MicroRNAs play a significant role in host-microbe interactions, and parasite microRNAs may affect the host's innate immunity. Furthermore, short RNAs are intriguing non-invasive biomarker possibilities because they can be found in physiological fluids. These trends suggest that for many researchers, quick and simple techniques for expression profiling and subsequent downstream analysis of miRNA-seq data are crucial. We selected sRNAtoolbox to make integrated sRNA research easier. Each tool can be used separately or to explore and analyze sRNAbench results in further depth. A special focus was placed on the tools' usability. We review available miRNA research tools to have an overview of the evaluation of the tools. Mainly we evaluate the tool sRNAtoolbox.
Topics: Animals; MicroRNAs; Software; Plants; Computational Biology; Sequence Analysis, RNA
PubMed: 38360000
DOI: 10.1016/bs.pmbts.2023.12.018