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1.
MicroRNAs and new biotechnological tools for its modulation and improving stress tolerance in plants.
Basso, MF, Ferreira, PCG, Kobayashi, AK, Harmon, FG, Nepomuceno, AL, Molinari, HBC, Grossi-de-Sa, MF
Plant biotechnology journal. 2019;(8):1482-1500
Abstract
MicroRNAs (miRNAs) modulate the abundance and spatial-temporal accumulation of target mRNAs and indirectly regulate several plant processes. Transcriptional regulation of the genes encoding miRNAs (MIR genes) can be activated by numerous transcription factors, which themselves are regulated by other miRNAs. Fine-tuning of MIR genes or miRNAs is a powerful biotechnological strategy to improve tolerance to abiotic or biotic stresses in crops of economic importance. Current approaches for miRNA fine-tuning are based on the down- or up-regulation of MIR gene transcription and the use of genetic engineering tools to manipulate the final concentration of these miRNAs in the cytoplasm. Transgenesis, cisgenesis, intragenesis, artificial MIR genes, endogenous and artificial target mimicry, MIR genes editing using Meganucleases, ZNF proteins, TALENs and CRISPR/Cas9 or CRISPR/Cpf1, CRISPR/dCas9 or dCpf1, CRISPR13a, topical delivery of miRNAs and epigenetic memory have been successfully explored to MIR gene or miRNA modulation and improve agronomic traits in several model or crop plants. However, advantages and drawbacks of each of these new biotechnological tools (NBTs) are still not well understood. In this review, we provide a brief overview of the biogenesis and role of miRNAs in response to abiotic or biotic stresses, we present critically the main NBTs used for the manipulation of MIR genes and miRNAs, we show current efforts and findings with the MIR genes and miRNAs modulation in plants, and we summarize the advantages and drawbacks of these NBTs and provide some alternatives to overcome. Finally, challenges and future perspectives to miRNA modulating in important crops are also discussed.
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Exploring miRNAs for developing climate-resilient crops: A perspective review.
Xu, J, Hou, QM, Khare, T, Verma, SK, Kumar, V
The Science of the total environment. 2019;:91-104
Abstract
Climate changes and environmental stresses have significant implications on global crop production and necessitate developing crops that can withstand an array of climate changes and environmental perturbations such as irregular water-supplies leading to drought or water-logging, hyper soil-salinity, extreme and variable temperatures, ultraviolet radiations and metal stress. Plants have intricate molecular mechanisms to cope with these dynamic environmental changes, one of the most common and effective being the reprogramming of expression of stress-responsive genes. Plant microRNAs (miRNAs) have emerged as key post-transcriptional and translational regulators of gene-expression for modulation of stress implications. Recent reports are establishing their key roles in epigenetic regulations of stress/adaptive responses as well as in providing plants genome-stability. Several stress responsive miRNAs are being identified from different crop plants and miRNA-driven RNA-interference (RNAi) is turning into a technology of choice for improving crop traits and providing phenotypic plasticity in challenging environments. Here we presents a perspective review on exploration of miRNAs as potent targets for engineering crops that can withstand multi-stress environments via loss-/gain-of-function approaches. This review also shed a light on potential roles plant miRNAs play in genome-stability and their emergence as potent target for genome-editing. Current knowledge on plant miRNAs, their biogenesis, function, their targets, and latest developments in bioinformatics approaches for plant miRNAs are discussed. Though there are recent reviews discussing primarily the individual miRNAs responsive to single stress factors, however, considering practical limitation of this approach, special emphasis is given in this review on miRNAs involved in responses and adaptation of plants to multi-stress environments including at epigenetic and/or epigenomic levels.
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3.
Micro(RNA)-managing muscle wasting.
Sannicandro, AJ, Soriano-Arroquia, A, Goljanek-Whysall, K
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(2):619-632
Abstract
Progressive skeletal muscle wasting is a natural consequence of aging and is common in chronic and acute diseases. Loss of skeletal muscle mass and function (strength) often leads to frailty, decreased independence, and increased risk of hospitalization. Despite progress made in our understanding of the mechanisms underlying muscle wasting, there is still no treatment available, with exercise training and dietary supplementation improving, but not restoring, muscle mass and/or function. There has been slow progress in developing novel therapies for muscle wasting, either during aging or disease, partially due to the complex nature of processes underlying muscle loss. The mechanisms of muscle wasting are multifactorial, with a combination of factors underlying age- and disease-related functional muscle decline. These factors include well-characterized changes in muscle such as changes in protein turnover and more recently described mechanisms such as autophagy or satellite cell senescence. Advances in transcriptomics and other high-throughput approaches have highlighted significant deregulation of skeletal muscle gene and protein levels during aging and disease. These changes are regulated at different levels, including posttranscriptional gene expression regulation by microRNAs. microRNAs, potent regulators of gene expression, modulate many processes in muscle, and microRNA-based interventions have been recently suggested as a promising new therapeutic strategy against alterations in muscle homeostasis. Here, we review recent developments in understanding the aging-associated mechanisms of muscle wasting and explore potential microRNA-based therapeutic avenues.
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4.
The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE.
Jun, S, Datta, S, Wang, L, Pegany, R, Cano, M, Handa, JT
Experimental eye research. 2019;:346-355
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Abstract
The accumulation of lipids within drusen, the epidemiologic link of a high fat diet, and the identification of polymorphisms in genes involved in lipid metabolism that are associated with disease risk, have prompted interest in the role of lipid abnormalities in AMD. Despite intensive investigation, our understanding of how lipid abnormalities contribute to AMD development remains unclear. Lipid metabolism is tightly regulated, and its dysregulation can trigger excess lipid accumulation within the RPE and Bruch's membrane. The high oxidative stress environment of the macula can promote lipid oxidation, impairing their original function as well as producing oxidation-specific epitopes (OSE), which unless neutralized, can induce unwanted inflammation that additionally contributes to AMD progression. Considering the multiple layers of lipid metabolism and inflammation, and the ability to simultaneously target multiple pathways, microRNA (miRNAs) have emerged as important regulators of many age-related diseases including atherosclerosis and Alzheimer's disease. These diseases have similar etiologic characteristics such as lipid-rich deposits, oxidative stress, and inflammation with AMD, which suggests that miRNAs might influence lipid metabolism in AMD. In this review, we discuss the contribution of lipids to AMD pathobiology and introduce how miRNAs might affect lipid metabolism during lesion development. Establishing how miRNAs contribute to lipid accumulation in AMD will help to define the role of lipids in AMD, and open new treatment avenues for this enigmatic disease.
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MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer.
Rahman, MM, Brane, AC, Tollefsbol, TO
Cells. 2019;(10)
Abstract
Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest epigenetic dysregulation in breast cancer pathogenesis though genomic instability is central to breast cancer hallmarks. Being reversible and plastic, epigenetic processes appear more amenable toward therapeutic intervention than the more unidirectional genetic alterations. In this review, we discuss the epigenetic reprogramming associated with breast cancer such as shuffling of DNA methylation, histone acetylation, histone methylation, and miRNAs expression profiles. As part of this, we illustrate how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades. As reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches, we also focus on the strategies for restoring the epistate that favor improved disease outcome and therapeutic intervention.
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The role of miRNA in somatic embryogenesis.
Siddiqui, ZH, Abbas, ZK, Ansari, MW, Khan, MN
Genomics. 2019;(5):1026-1033
Abstract
Somatic embryogenesis (SEG) is one of the best techniques for mass production of economically important plants. It is also used for the study of morphology, anatomy, physiology, genetics and molecular mechanism of embryo development. Somatic Embryos (SE) are bipolar structures that develop from a cell other than a gamete or zygote. SEG reflects the unique developmental potential of plant somatic cells, resulting in the transition of the differentiated somatic cells to embryogenic cells to follow the zygotic embryo stages. There are several biochemical and physiological processes that transformed a single somatic cell to a whole plant. SE studies provide insight into cell mechanisms governing the totipotency process in plants. Previously, in vitro studies have suggested the role of various regulatory genes in embryogenic transition that are triggered by plant hormones in response to stress. The omic studies identify the specific genes, transcripts, and proteins required for somatic embryogenesis development. MicroRNAs (miRNAs) are small, 19-24 nucleotides (nt), non-coding small RNA regulatory molecules controlling a large number of biological processes. In addition to their role in SEG, miRNAs play vital role in plant development, secondary metabolite synthesis and metabolism of macromolecules, hormone signal transduction, and tolerance of plants to biotic and abiotic stresses. During last decade several types of miRNAs involved in SEG have been reported. Among these miRNAs, miR156, miR162, miR166a, miR167, miR168, miR171a/b, miR171c, miR393, miR397 and miR398 played very active role during various stages of SEG. In this review, we highlighted the role of these as well as other miRNAs in some economically important plants.
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The latest progress on miR-374 and its functional implications in physiological and pathological processes.
Bian, H, Zhou, Y, Zhou, D, Zhang, Y, Shang, D, Qi, J
Journal of cellular and molecular medicine. 2019;(5):3063-3076
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Abstract
Non-coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non-coding RNAs (lncRNAs >200nt), stable non-coding RNAs (60-300nt), microRNAs (miRs or miRNAs, 18-24nt), circular RNAs, piwi-interacting RNAs (26-31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR-374 family member are located at the X-chromosome inactivation center. In recent years, numerous researches have uncovered that miR-374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR-374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.
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Gut-Amygdala Interactions in Autism Spectrum Disorders: Developmental Roles via regulating Mitochondria, Exosomes, Immunity and microRNAs.
Seo, M, Anderson, G
Current pharmaceutical design. 2019;(41):4344-4356
Abstract
BACKGROUND Autism Spectrum Disorders (ASD) have long been conceived as developmental disorder. A growing body of data highlights a role for alterations in the gut in the pathoetiology and/or pathophysiology of ASD. Recent work shows alterations in the gut microbiome to have a significant impact on amygdala development in infancy, suggesting that the alterations in the gut microbiome may act to modulate not only amygdala development but how the amygdala modulates the development of the frontal cortex and other brain regions. METHODS This article reviews wide bodies of data pertaining to the developmental roles of the maternal and foetal gut and immune systems in the regulation of offspring brain development. RESULTS A number of processes seem to be important in mediating how genetic, epigenetic and environmental factors interact in early development to regulate such gut-mediated changes in the amygdala, wider brain functioning and inter-area connectivity, including via regulation of microRNA (miR)-451, 14-3-3 proteins, cytochrome P450 (CYP)1B1 and the melatonergic pathways. As well as a decrease in the activity of monoamine oxidase, heightened levels of in miR-451 and CYP1B1, coupled to decreased 14-3-3 act to inhibit the synthesis of N-acetylserotonin and melatonin, contributing to the hyperserotonemia that is often evident in ASD, with consequences for mitochondria functioning and the content of released exosomes. These same factors are likely to play a role in regulating placental changes that underpin the association of ASD with preeclampsia and other perinatal risk factors, including exposure to heavy metals and air pollutants. Such alterations in placental and gut processes act to change the amygdala-driven biological underpinnings of affect-cognitive and affect-sensory interactions in the brain. CONCLUSION Such a perspective readily incorporates previously disparate bodies of data in ASD, including the role of the mu-opioid receptor, dopamine signaling and dopamine receptors, as well as the changes occurring to oxytocin and taurine levels. This has a number of treatment implications, the most readily applicable being the utilization of sodium butyrate and melatonin.
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MicroRNAs play an essential role in autophagy regulation in various disease phenotypes.
Zhao, Y, Wang, Z, Zhang, W, Zhang, L
BioFactors (Oxford, England). 2019;(6):844-856
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Abstract
Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well-organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post-transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA-based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy-related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.
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Activity of MCPIP1 RNase in tumor associated processes.
Miekus, K, Kotlinowski, J, Lichawska-Cieslar, A, Rys, J, Jura, J
Journal of experimental & clinical cancer research : CR. 2019;(1):421
Abstract
The monocyte chemoattractant protein-induced protein (MCPIP) family consists of 4 members (MCPIP1-4) encoded by the ZC3h12A-D genes, which are located at different loci. The common features of MCPIP proteins are the zinc finger domain, consisting of three cysteines and one histidine (CCCH), and the N-terminal domain of the PilT protein (PilT-N-terminal domain (PIN domain)). All family members act as endonucleases controlling the half-life of mRNA and microRNA (miRNA). The best-studied member of this family is MCPIP1 (also known as Regnase-1).In this review, we discuss the current knowledge on the role of MCPIP1 in cancer-related processes. Because the characteristics of MCPIP1 as a fundamental negative regulator of immune processes have been comprehensively described in numerous studies, we focus on the function of MCPIP1 in modulating apoptosis, angiogenesis and metastasis.