Shuo Deng, M. S. Ong, Zhi Xuan Ng, T. Jegadeesan, J. So, A. Kumar, C. Yap
Gastric cancer (GC) is one of the most prevalent cancers worldwide, with more than 700,000 cases of death. Histopathologically, GC can be classified into two main subtypes, the intestinal- and diffuse-type GC. These two subtypes differ not only in histological parameters, but also show distinct profiles of gene alternations. In this research highlight, we provide a summary of gene mutations in both the intestinal- and diffuse-type GC, and also highlight our recent findings on the role gelsolin, an actin-regulating protein, in GC dissemination. We recently found that gelsolin is differentially expressed in intestinal and diffuse type GC, and uncovered its involvement in the HGF/c-Met oncogenic pathway, which is a frequent activated signaling pathway in GC dissemination. Other roles of gelsolin in cancer development have also been discussed, with a focus on its potential link to oncogenic pathways and gene alternations in cancer metastasis. Our work provides a potential link between gelsolin and pro-invasive pathways in GC, and hence suggest a potential avenue for combating GC dissemination and metastasis with consideration of gelsolin status.
{"title":"Gelsolin: A new insight of its role on gastric cancer dissemination","authors":"Shuo Deng, M. S. Ong, Zhi Xuan Ng, T. Jegadeesan, J. So, A. Kumar, C. Yap","doi":"10.14800/RD.1439","DOIUrl":"https://doi.org/10.14800/RD.1439","url":null,"abstract":"Gastric cancer (GC) is one of the most prevalent cancers worldwide, with more than 700,000 cases of death. Histopathologically, GC can be classified into two main subtypes, the intestinal- and diffuse-type GC. These two subtypes differ not only in histological parameters, but also show distinct profiles of gene alternations. In this research highlight, we provide a summary of gene mutations in both the intestinal- and diffuse-type GC, and also highlight our recent findings on the role gelsolin, an actin-regulating protein, in GC dissemination. We recently found that gelsolin is differentially expressed in intestinal and diffuse type GC, and uncovered its involvement in the HGF/c-Met oncogenic pathway, which is a frequent activated signaling pathway in GC dissemination. Other roles of gelsolin in cancer development have also been discussed, with a focus on its potential link to oncogenic pathways and gene alternations in cancer metastasis. Our work provides a potential link between gelsolin and pro-invasive pathways in GC, and hence suggest a potential avenue for combating GC dissemination and metastasis with consideration of gelsolin status.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keita Tsujimura, Hideyuki Nakashima, K. Irie, K. Nakashima
Post-transcriptional regulation of gene expression is required for multiple aspects of neuronal development and function in the central nervous system. A sub-class of small non-coding RNA, called microRNAs (miRNAs), is emerging as key modulators of post-transcriptional gene regulation in numerous tissues, including the nervous system. Recent evidence has revealed a widespread role for miRNAs in various aspects of neuronal morphogenesis, including axogenesis, dendritogenesis, and synapse formation. Furthermore, dysregulation or altered expression of miRNAs has been associated with the pathogenesis of neurodevelopmental and psychiatric disorders. Here, we highlight recent advances in the study of miRNA-based regulation of neuronal development and their implications in neurological disorders.
{"title":"Emerging roles for miRNA-based post-transcriptional regulation in neuronal morphogenesis and neurodevelopmental disorders","authors":"Keita Tsujimura, Hideyuki Nakashima, K. Irie, K. Nakashima","doi":"10.14800/RD.1456","DOIUrl":"https://doi.org/10.14800/RD.1456","url":null,"abstract":"Post-transcriptional regulation of gene expression is required for multiple aspects of neuronal development and function in the central nervous system. A sub-class of small non-coding RNA, called microRNAs (miRNAs), is emerging as key modulators of post-transcriptional gene regulation in numerous tissues, including the nervous system. Recent evidence has revealed a widespread role for miRNAs in various aspects of neuronal morphogenesis, including axogenesis, dendritogenesis, and synapse formation. Furthermore, dysregulation or altered expression of miRNAs has been associated with the pathogenesis of neurodevelopmental and psychiatric disorders. Here, we highlight recent advances in the study of miRNA-based regulation of neuronal development and their implications in neurological disorders.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MiRNAs regulate gene expression post-transcriptionally and pre-translationally. Through gene regulation, several miRNAs have been found to play a significant role in various diseases. Each miRNA has multiple targets and is able to have a potent, albeit complex, effect on the cells. Specifically, miRNA-15a has been found to significantly reduce cancer cell survival and aggressiveness through multiple mechanisms across several cancer types. Our research found that miRNA-15a was able to decrease melanoma cell viability in-vitro and in-vivo. We have also found that miRNA-15a caused cell cycle arrest at the G0/G1 phase. Moreover, miRNA-15a was found to decrease the invasiveness of melanoma cells. CDCA4 was also discovered as a novel bona-fide target of miRNA-15a. The following oncogenic mRNAs are verified targets of miRNA-15a: CDCA4, BCL2L2, YAP1, AKT-3, Cyclin E1, and γ-Synuclein. In the future we hope to better understand which miRNAs will be effective in different transcriptome and genome environments. Efforts such as the NIH Center for Cancer Genomics' ‘The Cancer Genome Atlas,’ ‘Cancer Target and Driver Discovery Network,’ and the ‘Human Cancer Models Initiatives’ among others, will help us characterize the specific tumor environments in which different miRNAs are able to reduce cancer proliferation and aggression. This information will be enhanced by improving the delivery of miRNA by inducing its expression in-situ with dCas9 conjugated to activation domains.
{"title":"The anti-melanoma activity and oncogenic targets of hsa-miR-15a-5p","authors":"Christopher Alderman, Yixin Yang","doi":"10.14800/RD.1450","DOIUrl":"https://doi.org/10.14800/RD.1450","url":null,"abstract":"MiRNAs regulate gene expression post-transcriptionally and pre-translationally. Through gene regulation, several miRNAs have been found to play a significant role in various diseases. Each miRNA has multiple targets and is able to have a potent, albeit complex, effect on the cells. Specifically, miRNA-15a has been found to significantly reduce cancer cell survival and aggressiveness through multiple mechanisms across several cancer types. Our research found that miRNA-15a was able to decrease melanoma cell viability in-vitro and in-vivo. We have also found that miRNA-15a caused cell cycle arrest at the G0/G1 phase. Moreover, miRNA-15a was found to decrease the invasiveness of melanoma cells. CDCA4 was also discovered as a novel bona-fide target of miRNA-15a. The following oncogenic mRNAs are verified targets of miRNA-15a: CDCA4, BCL2L2, YAP1, AKT-3, Cyclin E1, and γ-Synuclein. In the future we hope to better understand which miRNAs will be effective in different transcriptome and genome environments. Efforts such as the NIH Center for Cancer Genomics' ‘The Cancer Genome Atlas,’ ‘Cancer Target and Driver Discovery Network,’ and the ‘Human Cancer Models Initiatives’ among others, will help us characterize the specific tumor environments in which different miRNAs are able to reduce cancer proliferation and aggression. This information will be enhanced by improving the delivery of miRNA by inducing its expression in-situ with dCas9 conjugated to activation domains.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84113011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, the impairment of RNA binding proteins that play key roles in the post-transcriptional regulation of gene expression has been linked to numerous neurological diseases. These RNA binding proteins perform critical mRNA processing steps in the nucleus, including splicing, polyadenylation, and export. In many cases, these RNA binding proteins are ubiquitously expressed raising key questions about why only brain function is impaired. Recently, mutations in the ZC3H14 gene, encoding an evolutionarily conserved, polyadenosine RNA binding protein, have been linked to a nonsyndromic form of autosomal recessive intellectual disability. Thus far, research on ZC3H14 and its Nab2 orthologs in budding yeast and Drosophila reveals that ZC3H14/Nab2 is important for mRNA processing and neuronal patterning. Two recent studies now provide evidence that ZC3H14/Nab2 may function in the quality control of mRNA splicing and export and could help to explain the molecular defects that cause neuronal dysfunction and lead to an inherited form of intellectual disability. These studies on ZC3H14/Nab2 reveal new clues to the puzzle of why loss of the ubiquitously expressed ZC3H14 protein specifically affects neurons.
{"title":"Links between mRNA splicing, mRNA quality control, and intellectual disability.","authors":"Milo B. Fasken, A. Corbett","doi":"10.14800/RD.1448","DOIUrl":"https://doi.org/10.14800/RD.1448","url":null,"abstract":"In recent years, the impairment of RNA binding proteins that play key roles in the post-transcriptional regulation of gene expression has been linked to numerous neurological diseases. These RNA binding proteins perform critical mRNA processing steps in the nucleus, including splicing, polyadenylation, and export. In many cases, these RNA binding proteins are ubiquitously expressed raising key questions about why only brain function is impaired. Recently, mutations in the ZC3H14 gene, encoding an evolutionarily conserved, polyadenosine RNA binding protein, have been linked to a nonsyndromic form of autosomal recessive intellectual disability. Thus far, research on ZC3H14 and its Nab2 orthologs in budding yeast and Drosophila reveals that ZC3H14/Nab2 is important for mRNA processing and neuronal patterning. Two recent studies now provide evidence that ZC3H14/Nab2 may function in the quality control of mRNA splicing and export and could help to explain the molecular defects that cause neuronal dysfunction and lead to an inherited form of intellectual disability. These studies on ZC3H14/Nab2 reveal new clues to the puzzle of why loss of the ubiquitously expressed ZC3H14 protein specifically affects neurons.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been conclusively proven that physical activity exerts beneficial effects on individual health. However, endurance activities in susceptible individuals can increase the risk of concerning cardiovascular conditions such as ventricular hypertrophy or arrhythmia. This increased risk can be attributed to a cardiac remodeling process specifically associated with endurance sports. In recent years, microRNAs (miRNAs) have been postulated to play many roles in health and disease. In the heart miRNAs regulate electrical remodeling, cardiac dilatation, fibrosis, calcium handling, heart failure, atrial fibrillation and autonomic tone in myocardial infarction. A growing body of evidence suggests that miRNAs also regulate endurance sports induced remodeling of the heart. Since miRNAs circulate in the blood they have a potential role as biomarkers in athletes indicating the degree of remodeling and predicting the risk of progression to an overt disease state.
{"title":"microRNA-mediated cardiac remodeling in athletes","authors":"S. Clauss, Ling Xiao, A. Hanley, T. Nickel","doi":"10.14800/RD.1442","DOIUrl":"https://doi.org/10.14800/RD.1442","url":null,"abstract":"It has been conclusively proven that physical activity exerts beneficial effects on individual health. However, endurance activities in susceptible individuals can increase the risk of concerning cardiovascular conditions such as ventricular hypertrophy or arrhythmia. This increased risk can be attributed to a cardiac remodeling process specifically associated with endurance sports. In recent years, microRNAs (miRNAs) have been postulated to play many roles in health and disease. In the heart miRNAs regulate electrical remodeling, cardiac dilatation, fibrosis, calcium handling, heart failure, atrial fibrillation and autonomic tone in myocardial infarction. A growing body of evidence suggests that miRNAs also regulate endurance sports induced remodeling of the heart. Since miRNAs circulate in the blood they have a potential role as biomarkers in athletes indicating the degree of remodeling and predicting the risk of progression to an overt disease state.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Postmortem molecular analysis of the human brain during development and aging suggests there are epigenetic changes reflecting early life experiences. This includes changes in the expression of non-coding RNAs such as microRNA. These molecules alter the regulation of gene expression and can interact with underlying genetic risk factors, contributing to neurological and neuropsychiatric syndromes such as schizophrenia. Recent evidence suggests that these dynamic and influential molecules play an important role in both brain development and the cellular response to stress. In our recent studies, we investigate the role of microRNA in the brains’ response to maternal immune activation and adolescent cannabinoid exposure, alone and in combination, as both have been identified as environmental risk factors for this disorder. We found that combined exposure to significantly altered microRNA expression in the left hemisphere of the entorhinal cortex as compared to the right. These changes were dominated by a large subgroup of microRNA transcribed from a single imprinted locus on chromosome 6q32 that is associated with schizophrenia. These changes correlated with altered gene expression in the combined treatment group, with microRNA-gene interactions predicted to regulate neuronal growth and differentiation; development of specific cortical layers; synaptic plasticity and transmission; axonogenesis; gamma-aminobutyric acid neurotransmitter system; and learning and memory formation. These findings suggested that the interaction of both an early and late environmental insult enhances changes in offspring microRNA expression in the brain with possible outcomes relevant to neurological disorders in adulthood.
{"title":"Small RNA regulation of neural gene expression in response to environmental exposure associated with neuropsychiatric syndromes","authors":"S. L. Hollins, F. Walker, M. Cairns","doi":"10.14800/RD.1382","DOIUrl":"https://doi.org/10.14800/RD.1382","url":null,"abstract":"Postmortem molecular analysis of the human brain during development and aging suggests there are epigenetic changes reflecting early life experiences. This includes changes in the expression of non-coding RNAs such as microRNA. These molecules alter the regulation of gene expression and can interact with underlying genetic risk factors, contributing to neurological and neuropsychiatric syndromes such as schizophrenia. Recent evidence suggests that these dynamic and influential molecules play an important role in both brain development and the cellular response to stress. In our recent studies, we investigate the role of microRNA in the brains’ response to maternal immune activation and adolescent cannabinoid exposure, alone and in combination, as both have been identified as environmental risk factors for this disorder. We found that combined exposure to significantly altered microRNA expression in the left hemisphere of the entorhinal cortex as compared to the right. These changes were dominated by a large subgroup of microRNA transcribed from a single imprinted locus on chromosome 6q32 that is associated with schizophrenia. These changes correlated with altered gene expression in the combined treatment group, with microRNA-gene interactions predicted to regulate neuronal growth and differentiation; development of specific cortical layers; synaptic plasticity and transmission; axonogenesis; gamma-aminobutyric acid neurotransmitter system; and learning and memory formation. These findings suggested that the interaction of both an early and late environmental insult enhances changes in offspring microRNA expression in the brain with possible outcomes relevant to neurological disorders in adulthood.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sydney Aten, Katelin F. Hansen, K. Hoyt, K. Obrietan
The microRNA (miRNA) class of small (typically 22–24 nt) non-coding RNA affects a wide range of physiological processes in the mammalian central nervous system (CNS). By acting as potent regulators of mRNA translation and stability, miRNAs fine-tune the expression of a multitude of genes that play critical roles in complex cognitive processes, including learning and memory. Of note, within the CNS, miRNAs can be expressed in an inducible, and cell-type specific manner. Here, we provide a brief overview of the expression and functional effects of the miR-132/212 gene locus in forebrain circuits of the CNS, and then discuss a recent publication that explored the contributions of miR-132 and miR-212 to cognition and to transcriptome regulation. We also discuss mechanisms by which synaptic activity regulates miR-132/212 expression, how miR-132 and miR-212 affect neuronal plasticity, and how the dysregulation of these two miRNAs could contribute to the development of cognitive impairments.
{"title":"The miR-132/212 locus: a complex regulator of neuronal plasticity, gene expression and cognition","authors":"Sydney Aten, Katelin F. Hansen, K. Hoyt, K. Obrietan","doi":"10.14800/RD.1375","DOIUrl":"https://doi.org/10.14800/RD.1375","url":null,"abstract":"The microRNA (miRNA) class of small (typically 22–24 nt) non-coding RNA affects a wide range of physiological processes in the mammalian central nervous system (CNS). By acting as potent regulators of mRNA translation and stability, miRNAs fine-tune the expression of a multitude of genes that play critical roles in complex cognitive processes, including learning and memory. Of note, within the CNS, miRNAs can be expressed in an inducible, and cell-type specific manner. Here, we provide a brief overview of the expression and functional effects of the miR-132/212 gene locus in forebrain circuits of the CNS, and then discuss a recent publication that explored the contributions of miR-132 and miR-212 to cognition and to transcriptome regulation. We also discuss mechanisms by which synaptic activity regulates miR-132/212 expression, how miR-132 and miR-212 affect neuronal plasticity, and how the dysregulation of these two miRNAs could contribute to the development of cognitive impairments.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80415262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ARS2 is a stable component of the nuclear cap-binding complex (CBC) and is critical for RNA Polymerase II transcript processing. Moreover, ARS2, and its orthologue SERRATE in plants, has been implicated in having a role in most established CBC-dependent functions. This review will provide insight into the functions of ARS2/SERRATE in numerous RNA Polymerase II transcript processing events, which happen co-transcriptionally from initiation to termination, and post-transcriptionally during maturation and export into the cytoplasm. Additionally, we will discuss what is known regarding ARS2/SERRATE structure in plants and in mammals.
{"title":"The diverse requirements of ARS2 in nuclear cap-binding complex-dependent RNA processing","authors":"Connor O’Sullivan, P. Howard","doi":"10.14800/RD.1376","DOIUrl":"https://doi.org/10.14800/RD.1376","url":null,"abstract":"ARS2 is a stable component of the nuclear cap-binding complex (CBC) and is critical for RNA Polymerase II transcript processing. Moreover, ARS2, and its orthologue SERRATE in plants, has been implicated in having a role in most established CBC-dependent functions. This review will provide insight into the functions of ARS2/SERRATE in numerous RNA Polymerase II transcript processing events, which happen co-transcriptionally from initiation to termination, and post-transcriptionally during maturation and export into the cytoplasm. Additionally, we will discuss what is known regarding ARS2/SERRATE structure in plants and in mammals.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Halman, Emily R Satterwhite, Jaclyn Smollett, Eckart Bindewald, Lorena Parlea, Mathias Viard, P. Zakrevsky, W. Kasprzak, K. Afonin, B. Shapiro
The targeted and conditional activation of pharmaceuticals is an increasingly important feature in modern personalized medicine. Nucleic acid nanoparticles show tremendous potential in this exploit due to their programmability and biocompatibility. Among the most powerful nucleic acid specific treatments is RNA interference-based therapeutics. RNA interference is a naturally occurring phenomenon in which specific genes are effectively silenced. Recently we have developed two different strategies based on customized multivalent nucleic acid nanoparticles with the ability to conditionally activate RNA interference in diseased cells as well as elicit detectable fluorescent responses.[1,2] These novel technologies can be further utilized for the simultaneous delivery and conditional intracellular activation of multiple therapeutic and biosensing functions to combat various diseases.
{"title":"Triggerable RNA nanodevices","authors":"J. Halman, Emily R Satterwhite, Jaclyn Smollett, Eckart Bindewald, Lorena Parlea, Mathias Viard, P. Zakrevsky, W. Kasprzak, K. Afonin, B. Shapiro","doi":"10.14800/RD.1349","DOIUrl":"https://doi.org/10.14800/RD.1349","url":null,"abstract":"The targeted and conditional activation of pharmaceuticals is an increasingly important feature in modern personalized medicine. Nucleic acid nanoparticles show tremendous potential in this exploit due to their programmability and biocompatibility. Among the most powerful nucleic acid specific treatments is RNA interference-based therapeutics. RNA interference is a naturally occurring phenomenon in which specific genes are effectively silenced. Recently we have developed two different strategies based on customized multivalent nucleic acid nanoparticles with the ability to conditionally activate RNA interference in diseased cells as well as elicit detectable fluorescent responses.[1,2] These novel technologies can be further utilized for the simultaneous delivery and conditional intracellular activation of multiple therapeutic and biosensing functions to combat various diseases.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88859934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNAs (miRNAs) are non-coding RNAs, approximately 22 nucleotides in length, that act as post-transcriptional regulators. Thousands of miRNAs have been identified in animals, and they are well conserved across species. MicroRNAs play essential regulatory roles in cellular processes, and changes in miRNA expression are associated with human diseases. Originally, miR-124 was identified as a brain-enriched miRNA and shown to be involved in brain and neuronal development. MiR-124 has since been reported to be expressed in other organs and to be involved in various biological phenomena. MiRNA-124 plays roles in various pathologic conditions, including cancers, acute stress, cardiovascular disorders, inflammatory responses, chronic pain, and osteoclast differentiation. MiR-124 has also been shown to suppress various tumor functions, including proliferation, activation, survival, invasion, metastasis, and migration. Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of unknown etiology, whose treatment has been significantly improved by the advent of biological drugs. Even so, some RA patients show little or no response to these therapies, suggesting the need for additional treatments. In a study comparing miRNA expression in RA and osteoarthritis (OA) fibroblast-like synoviocytes (FLS), we found that miR-124a was the only miRNA whose expression was lower in RA than in OA FLS.MiR-124a was found to directly downregulate the production of CDK-2 and MCP-1. In the rat adjuvant-induced arthritis (AIA) model, a single injection of pre-miR-124 into one ankle joint suppressed joint swelling in all of the limbs. Histological examination showed that AIA rats treated with pre-miR-124 exhibited reduced synoviocyte proliferation, less leucocyte infiltration into synovial tissue, and less cartilage and bone destruction than untreated AIA rats. The joints of the pre-miR-124-treated AIA rats also showed reduced osteoclast numbers and reduced RANKL, integrin β1 (ITGB1), and NFATc1 expression levels. MiR-124 was shown to directly target the 3’UTRs of the rat NFATc1, ITGB1, SP1, and CEBPα mRNAs. Both miR-124 and miR-124a were also found to directly target human NFATc1 mRNA and to suppress the differentiation of human osteoclasts from monocytes. Taken together, recent studies suggest that MiR-124 may be a promising therapeutic agent for RA and other diseases.
{"title":"MicroRNA-124: A promising therapeutic agent for various human diseases, including rheumatoid arthritis.","authors":"Y. Nakamachi, J. Saegusa, S. Kawano","doi":"10.14800/RD.1252","DOIUrl":"https://doi.org/10.14800/RD.1252","url":null,"abstract":"MicroRNAs (miRNAs) are non-coding RNAs, approximately 22 nucleotides in length, that act as post-transcriptional regulators. Thousands of miRNAs have been identified in animals, and they are well conserved across species. MicroRNAs play essential regulatory roles in cellular processes, and changes in miRNA expression are associated with human diseases. Originally, miR-124 was identified as a brain-enriched miRNA and shown to be involved in brain and neuronal development. MiR-124 has since been reported to be expressed in other organs and to be involved in various biological phenomena. MiRNA-124 plays roles in various pathologic conditions, including cancers, acute stress, cardiovascular disorders, inflammatory responses, chronic pain, and osteoclast differentiation. MiR-124 has also been shown to suppress various tumor functions, including proliferation, activation, survival, invasion, metastasis, and migration. Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of unknown etiology, whose treatment has been significantly improved by the advent of biological drugs. Even so, some RA patients show little or no response to these therapies, suggesting the need for additional treatments. In a study comparing miRNA expression in RA and osteoarthritis (OA) fibroblast-like synoviocytes (FLS), we found that miR-124a was the only miRNA whose expression was lower in RA than in OA FLS.MiR-124a was found to directly downregulate the production of CDK-2 and MCP-1. In the rat adjuvant-induced arthritis (AIA) model, a single injection of pre-miR-124 into one ankle joint suppressed joint swelling in all of the limbs. Histological examination showed that AIA rats treated with pre-miR-124 exhibited reduced synoviocyte proliferation, less leucocyte infiltration into synovial tissue, and less cartilage and bone destruction than untreated AIA rats. The joints of the pre-miR-124-treated AIA rats also showed reduced osteoclast numbers and reduced RANKL, integrin β1 (ITGB1), and NFATc1 expression levels. MiR-124 was shown to directly target the 3’UTRs of the rat NFATc1, ITGB1, SP1, and CEBPα mRNAs. Both miR-124 and miR-124a were also found to directly target human NFATc1 mRNA and to suppress the differentiation of human osteoclasts from monocytes. Taken together, recent studies suggest that MiR-124 may be a promising therapeutic agent for RA and other diseases.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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