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Balkan Medical Journal Feb 2020Cardiovascular diseases are one of the most common causes of death in both developing and developed countries worldwide. Even though there have been improvements in...
Cardiovascular diseases are one of the most common causes of death in both developing and developed countries worldwide. Even though there have been improvements in primary prevention, the prevalence of cardiovascular diseases continues to increase in recent years. Hence, it is crucial to both investigate the molecular pathophysiology of cardiovascular diseases in-depth and find novel biomarkers regarding the early and proper prevention and diagnosis of these diseases. MicroRNAs, or miRNAs, are endogenous, conserved, single-stranded non-coding RNAs of 21-25 nucleotides in length. miRNAs have important roles in various cellular events such as embryogenesis, proliferation, vasculogenesis, apoptosis, cell growth, differentiation, and tumorigenesis. They also have potential roles in the cardiovascular system, including angiogenesis, cardiac cell contractility, control of lipid metabolism, plaque formation, the arrangement of cardiac rhythm, and cardiac cell growth. Circulating miRNAs are promising novel biomarkers for purposes of the diagnosis and prognosis of cardiovascular diseases. Cell or tissue specificity, stability in serum or plasma, resistance to degradative factors such as freeze-thaw cycles or enzymes in the blood, and fast-release kinetics, provide the potential for miRNAs to be surrogate markers for the early and accurate diagnosis of disease and for predicting middle- or long-term prognosis. Moreover, it may be a logical approach to combine miRNAs with traditional biomarkers to improve risk stratification and long-term prognosis. In addition to their efficacy in both diagnosis and prognosis, miRNA-based therapeutics may be beneficial for treating cardiovascular diseases using novel platforms and computational tools and in combination with traditional methods of analysis. microRNAs are promising, novel therapeutic agents, which can affect multiple genes using different signaling pathways. miRNAs therapeutic modulation techniques have been used in the settings of atherosclerosis, acute myocardial infarction, restenosis, vascular remodeling, arrhythmias, hypertrophy and fibrosis, angiogenesis and cardiogenesis, aortic aneurysm, pulmonary hypertension, and ischemic injury. This review presents detailed information about miRNAs regarding structure and biogenesis, stages of synthesis and functions, expression profiles in serum/plasma of living organisms, diagnostic and prognostic potential as novel biomarkers, and therapeutic applications in various diseases.
Topics: Biomarkers; Cardiovascular Diseases; Humans; MicroRNAs; Prognosis
PubMed: 32018347
DOI: 10.4274/balkanmedj.galenos.2020.2020.1.94 -
Journal of Bone and Mineral Metabolism May 2023Bone metastasis is a common complication in several solid cancers, including breast, prostate, and lung. In the bone microenvironment, metastatic cancer cells disturb... (Review)
Review
Bone metastasis is a common complication in several solid cancers, including breast, prostate, and lung. In the bone microenvironment, metastatic cancer cells disturb bone homeostasis leading to osteolytic or osteosclerotic lesions. Osteolytic lesions are characterized by an increased osteoclast-mediated bone resorption while osteosclerotic lesions are caused by enhanced activity of osteoblasts and formation of poor-quality bone. A common feature in bone metastasis is the complex interplay between the cancer cells and the cells of the bone microenvironment, which can occur already before the cancer cells enter the distant site. Cancer cells at the primary site can secrete soluble factors and extracellular vesicles to bone to create a "pre-metastatic niche" i.e., prime the microenvironment permissive for cancer cell homing, survival, and growth. Once in the bone, cancer cells secrete factors to activate the osteoclasts or osteoblasts and the so called "vicious cycle of bone metastases". These pathological cell-cell interactions are largely dependent on secreted proteins. However, increasing evidence demonstrates that secreted RNA molecules, in particular small non-coding microRNAs are critical mediators of the crosstalk between bone and cancer cells. This review article discusses the role of secreted miRNAs in bone metastasis development and progression, and their potential as non-invasive biomarkers.
Topics: Male; Humans; MicroRNAs; Bone Neoplasms; Bone and Bones; Osteoclasts; Osteoblasts; Osteolysis; Tumor Microenvironment
PubMed: 37031329
DOI: 10.1007/s00774-023-01424-z -
Wiley Interdisciplinary Reviews. RNA Mar 2023An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA... (Review)
Review
An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA clusters. Even though many miRNA clusters have been greatly studied, most attention has been usually focused on functional impacts of clustered miRNA co-expression. However, there is also another compelling aspect about these miRNA clusters, their polycistronic nature. Being transcribed on a single RNA precursor, polycistronic miRNAs benefit from common transcriptional regulation allowing their coordinated expression. And yet, numerous reports have revealed striking discrepancies in the accumulation of mature miRNAs produced from the same cluster. Indeed, the larger polycistronic transcripts can act as platforms providing unforeseen post-transcriptional regulatory mechanisms controlling individual miRNA processing, thus leading to differential miRNA expression, and sometimes even challenging the general assumption that polycistronic miRNAs are co-expressed. In this review, we aim to address the current knowledge about how miRNA polycistrons are post-transcriptionally regulated. In particular, we will focus on the mechanisms occurring at the level of the primary transcript, which are highly relevant for individual miRNA processing and as such have a direct repercussion on miRNA function within the cell. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: Animals; MicroRNAs; Gene Expression Regulation; RNA Processing, Post-Transcriptional; RNA Interference
PubMed: 35702737
DOI: 10.1002/wrna.1749 -
International Journal of Molecular... Jun 2023Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to... (Review)
Review
Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to right ventricular failure and, consequently, to death. The most common causes of PH include left heart disease and lung disease. Despite the significant development of medicine and related sciences observed in recent years, we still suffer from a lack of effective treatment that would significantly influence the prognosis and prolong life expectancy of patients with PH. One type of PH is pulmonary arterial hypertension (PAH). The pathophysiology of PAH is based on increased cell proliferation and resistance to apoptosis in the small pulmonary arteries, leading to pulmonary vascular remodeling. However, studies conducted in recent years have shown that epigenetic changes may also lie behind the pathogenesis of PAH. Epigenetics is the study of changes in gene expression that are not related to changes in the sequence of nucleotides in DNA. In addition to DNA methylation or histone modification, epigenetic research focuses on non-coding RNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Preliminary research results give hope that targeting epigenetic regulators may lead to new, potential therapeutic possibilities in the treatment of PAH.
Topics: Humans; MicroRNAs; Pulmonary Arterial Hypertension; RNA, Long Noncoding; Lung; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Pulmonary Artery
PubMed: 37298685
DOI: 10.3390/ijms24119735 -
Bone Apr 2021microRNAs have evolved as important regulators of multiple biological pathways essential for bone homeostasis, and microRNA research has furthered our understanding of... (Review)
Review
microRNAs have evolved as important regulators of multiple biological pathways essential for bone homeostasis, and microRNA research has furthered our understanding of the mechanisms underlying bone health and disease. This knowledge, together with the finding that active or passive release of microRNAs from cells into the extracellular space enables minimal-invasive detection in biofluids (circulating miRNAs), motivated researchers to explore microRNAs as biomarkers in several pathologic conditions, including bone diseases. Thus, exploratory studies in cohorts representing different types of bone diseases have been performed. In this review, we first summarize important molecular basics of microRNA function and release and provide recommendations for best (pre-)analytical practices and documentation standards for circulating microRNA research required for generating high quality data and ensuring reproducibility of results. Secondly, we review how the genesis of bone-derived circulating microRNAs via release from osteoblasts and osteoclasts could contribute to the communication between these cells. Lastly, we summarize evidence from clinical research studies that have investigated the clinical utility of microRNAs as biomarkers in musculoskeletal disorders. While previous reviews have mainly focused on diagnosis of primary osteoporosis, we have also included studies exploring the utility of circulating microRNAs in monitoring anti-osteoporotic treatment and for diagnosis of other types of bone diseases, such as diabetic osteopathy, bone degradation in inflammatory diseases, and monogenetic bone diseases.
Topics: Biomarkers; Bone Density; Bone and Bones; Circulating MicroRNA; MicroRNAs; Reproducibility of Results
PubMed: 33301964
DOI: 10.1016/j.bone.2020.115787 -
Ageing Research Reviews May 2022Spinal stenosis is a common degenerative spine disorder in the aged population and the spinal ligament aging is a main contributor to this chronic disease. However, the... (Review)
Review
Spinal stenosis is a common degenerative spine disorder in the aged population and the spinal ligament aging is a main contributor to this chronic disease. However, the underlying mechanisms of spinal ligament aging remain unclear. Epigenetics is the study of heritable and reversible changes in the function of a gene or genome that occur without any alteration in the primary DNA sequence. Epigenetic alterations have been demonstrated to play crucial roles in age-related diseases and conditions, and they are recently studied as biomarkers and therapeutic targets in the field of cancer research. The main epigenetic modifications, including DNA methylation alteration, histone modifications as well as dysregulated noncoding RNA modulation, have all been implicated in spinal ligament aging diseases. DNA methylation modulates the expression of critical genes including WNT5A, GDNF, ACSM5, miR-497 and miR-195 during spinal ligament degeneration. Histone modifications widely affect gene expression and obvious histone modification abnormalities have been found in spinal ligament aging. MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) exert crucial regulating effects on spinal ligament aging conditions via targeting various osteogenic or fibrogenic differentiation related genes. To our knowledge, there is no systematic review yet to summarize the involvement of epigenetic mechanisms of spinal ligament aging in degenerative spinal diseases. In this study, we systematically discussed the different epigenetic modifications and their potential functions in spinal ligament aging process.
Topics: Aged; Aging; DNA Methylation; Epigenesis, Genetic; Humans; Ligaments; MicroRNAs; Spine
PubMed: 35218968
DOI: 10.1016/j.arr.2022.101598 -
RNA Biology Jan 2024MicroRNAs are a class of small regulatory RNAs that mediate regulation of protein synthesis by recognizing sequence elements in mRNAs. MicroRNAs are processed through a... (Review)
Review
MicroRNAs are a class of small regulatory RNAs that mediate regulation of protein synthesis by recognizing sequence elements in mRNAs. MicroRNAs are processed through a series of steps starting from transcription and primary processing in the nucleus to precursor processing and mature function in the cytoplasm. It is also in the cytoplasm where levels of mature microRNAs can be modulated through decay mechanisms. Here, we review the recent progress in the lifetime of a microRNA at all steps required for maintaining their homoeostasis. The increasing knowledge about microRNA regulation upholds great promise as therapeutic targets.
Topics: MicroRNAs; RNA, Messenger; Protein Biosynthesis; Ribonuclease III
PubMed: 38031325
DOI: 10.1080/15476286.2023.2288741 -
Briefings in Functional Genomics Mar 2021Glaucoma is a disease with characteristic optic neuropathy and loss of vision, leading to blindness, and primary open-angle glaucoma (POAG) is the most common glaucoma... (Review)
Review
Glaucoma is a disease with characteristic optic neuropathy and loss of vision, leading to blindness, and primary open-angle glaucoma (POAG) is the most common glaucoma type throughout the world. Genetic susceptibility is the main factor in POAG, and most susceptibility genes cause changes in microRNA expression and function, thereby leading to POAG occurrence and development. Increasing evidence indicates that many microRNAs are involved in the regulation of intraocular pressure (IOP) and play an important role in the increase in IOP in POAG. Additionally, microRNA is closely related to optic nerve damage factors (mechanical stress, hypoxia and inflammation). This review discusses the effect of single-nucleotide polymorphisms in POAG-related genes on microRNA and the value of microRNA in the diagnosis and treatment of POAG.
Topics: Genetic Predisposition to Disease; Glaucoma, Open-Angle; Humans; Intraocular Pressure; MicroRNAs; Polymorphism, Single Nucleotide
PubMed: 33165516
DOI: 10.1093/bfgp/elaa020 -
Advances in Clinical and Experimental... 2016Hepatocellular carcinoma is one of the deadliest types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor and there is... (Review)
Review
Hepatocellular carcinoma is one of the deadliest types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor and there is an urgent need for development of targeted therapies. MicroRNAs represent a class of small RNAs, frequently deregulated in human malignancies. We are reviewing the role of microRNA in the development of primary hepatocellular carcinoma and its use as a biomarker for early diagnosis and clinical treatment. First, we describe the current incidence and possible causes of the incidence of hepatocellular carcinoma, followed by the introduction of microRNA synthesis, maturation and function, and finally we explain the role of microRNA in the development of hepatocellular carcinoma and its clinical value as a biological marker in the diagnosis and treatment of liver cancer. A comprehensive analysis of cellular microRNA is a benefit for early diagnosis of hepatocellular carcinoma and early clinical intervention, and microRNA is considered by some to be a key target of gene therapy to control the occurrence and development of hepatocellular carcinoma..
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; MicroRNAs; Neoplasm Metastasis
PubMed: 28028963
DOI: 10.17219/acem/36460 -
Seminars in Cell & Developmental Biology Oct 2014The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional... (Review)
Review
The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional mechanisms: (i) by promoting decay of unstable mRNAs and (ii) by favoring maturation from precursors of select microRNAs (miRNAs) including the prototypical tumor suppressor let-7. Studies performed in primary and cultured cells as well as in mice proved that the ability of KSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response.
Topics: Animals; Cell Differentiation; Cytokines; Gene Expression Regulation; Genes, MHC Class II; Humans; Lipid Metabolism; MicroRNAs; RNA Stability; RNA, Messenger; RNA-Binding Proteins; Trans-Activators
PubMed: 24845017
DOI: 10.1016/j.semcdb.2014.05.004