Natural antisense transcripts (asRNAs) transcribed from eukaryotic genes are primarily long transcripts that do not code for proteins. Transcriptome analyses have revealed that asRNAs exhibit diverse functional roles in the regulation of gene expression. In the case of inducible genes, asRNAs epigenetically affect their expression or post-transcriptionally affect stability and translatability of their mRNAs. Many low-copy-number asRNAs regulate the expression levels of mRNAs through cis -controlling elements in the mRNA in concert with trans -acting factors, such as RNA-binding proteins and microRNAs. Recently, a competitive endogenous RNA (ceRNA) hypothesis was postulated as the basis of a functional network, comprising mRNAs, asRNAs, and microRNAs. This network finely tunes mRNA expression by common microRNA-responsive elements being present among mRNAs and asRNAs, permitting the redirection of microRNAs between the two. Examples of the ceRNA-mediated cross-regulation of mRNA expression are observed in the phosphatase and tensin homolog mRNA network and the interferon-alpha1 mRNA network. In such regulatory RNA networks, an mRNA, its corresponding asRNAs (high specificity), microRNAs (low specificity), and RNA-binding proteins mutually interact. Both asRNAs and microRNAs are involved in the pathogenesis or pathophysiology of various diseases, such as cancer, inflammation, and infection. Simple disruption of an asRNA or a microRNA can often show off-target effects due to complicated interactions inside and outside the regulatory RNA networks. Therefore, drugs that target asRNAs should be developed to minimize off-target effects and to target interactions that are dysregulated in disease.
{"title":"RNA Networks that Regulate mRNA Expression and their Potential as Drug Targets","authors":"M. Nishizawa, Tominori Kimura","doi":"10.14800/RD.864","DOIUrl":"https://doi.org/10.14800/RD.864","url":null,"abstract":"Natural antisense transcripts (asRNAs) transcribed from eukaryotic genes are primarily long transcripts that do not code for proteins. Transcriptome analyses have revealed that asRNAs exhibit diverse functional roles in the regulation of gene expression. In the case of inducible genes, asRNAs epigenetically affect their expression or post-transcriptionally affect stability and translatability of their mRNAs. Many low-copy-number asRNAs regulate the expression levels of mRNAs through cis -controlling elements in the mRNA in concert with trans -acting factors, such as RNA-binding proteins and microRNAs. Recently, a competitive endogenous RNA (ceRNA) hypothesis was postulated as the basis of a functional network, comprising mRNAs, asRNAs, and microRNAs. This network finely tunes mRNA expression by common microRNA-responsive elements being present among mRNAs and asRNAs, permitting the redirection of microRNAs between the two. Examples of the ceRNA-mediated cross-regulation of mRNA expression are observed in the phosphatase and tensin homolog mRNA network and the interferon-alpha1 mRNA network. In such regulatory RNA networks, an mRNA, its corresponding asRNAs (high specificity), microRNAs (low specificity), and RNA-binding proteins mutually interact. Both asRNAs and microRNAs are involved in the pathogenesis or pathophysiology of various diseases, such as cancer, inflammation, and infection. Simple disruption of an asRNA or a microRNA can often show off-target effects due to complicated interactions inside and outside the regulatory RNA networks. Therefore, drugs that target asRNAs should be developed to minimize off-target effects and to target interactions that are dysregulated in disease.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658126","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}
Wanpei Cai, Chao Wang, J. N. Goh, S. Loo, C. Yap, A. Kumar
The roles of non-coding RNAs in cancers, microRNA (miRNA) especially, have sparked interest in the field of RNA research in recent years. The once widely accepted ‘central dogma of genetics’ describing the flow of cellular protein expression is now being challenged following the discovery of non-coding RNA research. miRNAs belong to the family of non-coding RNAs, in which many have been shown to be involved in cancer progression, including breast cancer. Goh et al. have recently summarized comprehensively, the roles of miRNAs in the hallmarks of breast cancer progression. In this research highlight, we provide a brief summary of these miRNA-associated hallmarks in breast cancer progression and also highlight on a family of proteins known as DEAD-box RNA helicases, many of which have been found to be associated with miRNA-associated tumorigenesis. There are an increasing number of studies on DEAD-box RNA helicases in recent years, with different roles being reported in numerous cancer types. DDX20, a member of the DEAD-box RNA helicase family, was most recently identified by our group to be involved in breast cancer progression and metastasis. New data from our group found a possible novel miRNA-processing role of DDX20 in breast cancer. In an ongoing study, we found miRNA miR-222 expression inversely correlates with DDX20, suggesting a possible tumor suppressor role of miR-222 in invasive breast cancers, contrary to previous reports where miR-222 was associated with invasion in breast cancers. Our work thus provides another dimension to the complexity, where miRNAs and DEAD-box RNA helicases play in breast cancers.
{"title":"DEAD-box RNA Helicases: the microRNA managers of breast cancer","authors":"Wanpei Cai, Chao Wang, J. N. Goh, S. Loo, C. Yap, A. Kumar","doi":"10.14800/RD.846","DOIUrl":"https://doi.org/10.14800/RD.846","url":null,"abstract":"The roles of non-coding RNAs in cancers, microRNA (miRNA) especially, have sparked interest in the field of RNA research in recent years. The once widely accepted ‘central dogma of genetics’ describing the flow of cellular protein expression is now being challenged following the discovery of non-coding RNA research. miRNAs belong to the family of non-coding RNAs, in which many have been shown to be involved in cancer progression, including breast cancer. Goh et al. have recently summarized comprehensively, the roles of miRNAs in the hallmarks of breast cancer progression. In this research highlight, we provide a brief summary of these miRNA-associated hallmarks in breast cancer progression and also highlight on a family of proteins known as DEAD-box RNA helicases, many of which have been found to be associated with miRNA-associated tumorigenesis. There are an increasing number of studies on DEAD-box RNA helicases in recent years, with different roles being reported in numerous cancer types. DDX20, a member of the DEAD-box RNA helicase family, was most recently identified by our group to be involved in breast cancer progression and metastasis. New data from our group found a possible novel miRNA-processing role of DDX20 in breast cancer. In an ongoing study, we found miRNA miR-222 expression inversely correlates with DDX20, suggesting a possible tumor suppressor role of miR-222 in invasive breast cancers, contrary to previous reports where miR-222 was associated with invasion in breast cancers. Our work thus provides another dimension to the complexity, where miRNAs and DEAD-box RNA helicases play in breast cancers.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657445","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}
The perspective of disease development can often be attributed for deregulation of gene expression. Hepatocellular carcinoma (HCC) is the one of most common malignancies worldwide and chronic Hepatitis B Virus (HBV) infection is one of the major risk factors in development of HCC. Information about microRNA mediated regulation of viral infections is just emerging. MicroRNAs are about 19- 23 base pair long functional transcripts that regulate gene expression by cleavage or translational repression of target mRNA. Oncogenic (or tumor suppressive) roles of miRNA in many aspects of cancer biology and wide spread differential expression of miRNAs in different stages of HBV related Hepatocellular Carcinoma (HCC) compared with normal tissues are well documented. During HBV infection, perturbations of miRNA expression particularly cell cycle regulating miRNAs might have significant correlation with HCC development. Hepatitis B virus X protein (HBx) is a multifunctional protein that balances cell proliferation and programmed cell death by its anti and pro-apoptotic function. It affects transcriptional activation via its interaction with nuclear transcription factors as also cytoplasmic modulation in various signal transduction pathways contributing to cell proliferation and survival. HBx is often referred as oncoprotein for its crucial role in the development of HCC. HBx-miRNA interaction in HBV related HCC was the focus of much attention over last few years. HBx is found to modulate several miRNAs that are associated with HBV related HCC. This review concentrates on the interaction of HBx protein with some of the miRNAs that are essentially associated with cell proliferation and found modulated in HCC. HBx-miRNA interactions provide new insight into possible way by which viral protein acts through microRNA and thereby regulate host functioning. Finally, the HBx-miRNA interaction can be utilized as a therapeutic strategy for management of HBV related HCC.
{"title":"An insight into interaction of cell cycle regulating miRNAs and Hepatitis B virus X protein","authors":"M. Bandopadhyay, R. Chakravarty","doi":"10.14800/RD.818","DOIUrl":"https://doi.org/10.14800/RD.818","url":null,"abstract":"The perspective of disease development can often be attributed for deregulation of gene expression. Hepatocellular carcinoma (HCC) is the one of most common malignancies worldwide and chronic Hepatitis B Virus (HBV) infection is one of the major risk factors in development of HCC. Information about microRNA mediated regulation of viral infections is just emerging. MicroRNAs are about 19- 23 base pair long functional transcripts that regulate gene expression by cleavage or translational repression of target mRNA. Oncogenic (or tumor suppressive) roles of miRNA in many aspects of cancer biology and wide spread differential expression of miRNAs in different stages of HBV related Hepatocellular Carcinoma (HCC) compared with normal tissues are well documented. During HBV infection, perturbations of miRNA expression particularly cell cycle regulating miRNAs might have significant correlation with HCC development. Hepatitis B virus X protein (HBx) is a multifunctional protein that balances cell proliferation and programmed cell death by its anti and pro-apoptotic function. It affects transcriptional activation via its interaction with nuclear transcription factors as also cytoplasmic modulation in various signal transduction pathways contributing to cell proliferation and survival. HBx is often referred as oncoprotein for its crucial role in the development of HCC. HBx-miRNA interaction in HBV related HCC was the focus of much attention over last few years. HBx is found to modulate several miRNAs that are associated with HBV related HCC. This review concentrates on the interaction of HBx protein with some of the miRNAs that are essentially associated with cell proliferation and found modulated in HCC. HBx-miRNA interactions provide new insight into possible way by which viral protein acts through microRNA and thereby regulate host functioning. Finally, the HBx-miRNA interaction can be utilized as a therapeutic strategy for management of HBV related HCC.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657383","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}
F. Potus, M. Leguen, S. Provencher, J. Meloche, S. Bonnet
Over the last years, small non-coding microRNAs (miRNAs) have emerged as central actors of PAH etiology. Strong miRNA expression disorders occur in lungs as well as in right ventricle (RV) of PAH patients, which respectively lead to vascular remodeling of the distal pulmonary arteries and to RV failure. On the other hand, our understanding of PAH physiopathology has recently increased with the implication of DNA damage and DNA damage response (DDR) in this disease. Interestingly, DDR was described as a regulator of miRNA processing in both healthy and pathological conditions. In this review, we will first summarize miRNA expression impaired in lung and RV of PAH patients, then we will provide evidence that DDR could be at origin of miRNA pathway defects observed in pulmonary hypertension.
{"title":"DNA damage at the dawn of micro-RNA pathway impairment in pulmonary arterial hypertension","authors":"F. Potus, M. Leguen, S. Provencher, J. Meloche, S. Bonnet","doi":"10.14800/RD.810","DOIUrl":"https://doi.org/10.14800/RD.810","url":null,"abstract":"Over the last years, small non-coding microRNAs (miRNAs) have emerged as central actors of PAH etiology. Strong miRNA expression disorders occur in lungs as well as in right ventricle (RV) of PAH patients, which respectively lead to vascular remodeling of the distal pulmonary arteries and to RV failure. On the other hand, our understanding of PAH physiopathology has recently increased with the implication of DNA damage and DNA damage response (DDR) in this disease. Interestingly, DDR was described as a regulator of miRNA processing in both healthy and pathological conditions. In this review, we will first summarize miRNA expression impaired in lung and RV of PAH patients, then we will provide evidence that DDR could be at origin of miRNA pathway defects observed in pulmonary hypertension.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657328","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}
Female mosquitoes require a blood meal for reproduction, providing the underlying mechanism for the spread of many devastating vector-borne diseases in humans. Understanding the mechanisms that govern the major functions linked to the female mosquito's ability to utilize blood and develop eggs is of paramount importance. Reports have indicated that microRNAs (miRNAs) are differentially expressed in various tissues of the female mosquito upon the uptake of a blood meal. In our previous research, we have reported the importance of miRNAs in regulating mosquito blood digestion through the characterization of the conserved miRNA, miR-275, and the mosquito specific miRNA, miR-1174. Our most recent work has shown that the conserved miRNA, miR-8, targets the Wingless signaling pathway to regulate secretion of yolk protein precursors by the female mosquito fat body and accumulation into the developing ovaries. Here, we summarize the role of miRNAs in the female mosquito, particularly miR-8. We also discuss the recent advances in mosquito biology and how these genetic tools can enhance our understanding of miRNA function.
{"title":"Spatiotemporal analysis of microRNA-8 reveals important role in mosquito reproductive processes","authors":"Keira J. Lucas, A. Raikhel","doi":"10.14800/RD.815","DOIUrl":"https://doi.org/10.14800/RD.815","url":null,"abstract":"Female mosquitoes require a blood meal for reproduction, providing the underlying mechanism for the spread of many devastating vector-borne diseases in humans. Understanding the mechanisms that govern the major functions linked to the female mosquito's ability to utilize blood and develop eggs is of paramount importance. Reports have indicated that microRNAs (miRNAs) are differentially expressed in various tissues of the female mosquito upon the uptake of a blood meal. In our previous research, we have reported the importance of miRNAs in regulating mosquito blood digestion through the characterization of the conserved miRNA, miR-275, and the mosquito specific miRNA, miR-1174. Our most recent work has shown that the conserved miRNA, miR-8, targets the Wingless signaling pathway to regulate secretion of yolk protein precursors by the female mosquito fat body and accumulation into the developing ovaries. Here, we summarize the role of miRNAs in the female mosquito, particularly miR-8. We also discuss the recent advances in mosquito biology and how these genetic tools can enhance our understanding of miRNA function.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657372","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}
Breast cancer represents the leading cause of death in women worldwide. Ionizing radiation is one of the most relevant therapeutic approaches for the treatment of this type of cancer. Unfortunately, either resistance of tumor cells to therapeutic doses of radiation or normal tissue tolerance have proven to limit the effectiveness of radiotherapy. In the last few years, several studies have highlighted an important link between radioresistance, cancer and microRNAs (miRNAs), an emerging class of endogenous non coding RNAs that control gene expression at post-transcriptional/translational level. MiRNAs may influence carcinogenesis at multiple stages and effectively control tumor radiosensitivity as they affect levels of DNA damage repair, cell cycle checkpoint, apoptosis, radio-related signal transduction pathways and tumor microenvironment-related genes. Since radiation- and multidrug resistances are the characteristic properties of numerous type of tumors, there is increasing interest in establishing a clear association between miRNA expression in tumors and chemo- or radio-sensitivity, with regard to predicting or modulating sensitivity. In the present review, we summarize the emerging evidence of miRNA involvement in the radioresponse of breast tumors and discuss their potential as radiosensitizers.
{"title":"Emerging role of microRNAs in breast cancer radiotherapy","authors":"G. Marvaso, A. Barone, N. Amodio","doi":"10.14800/RD.786","DOIUrl":"https://doi.org/10.14800/RD.786","url":null,"abstract":"Breast cancer represents the leading cause of death in women worldwide. Ionizing radiation is one of the most relevant therapeutic approaches for the treatment of this type of cancer. Unfortunately, either resistance of tumor cells to therapeutic doses of radiation or normal tissue tolerance have proven to limit the effectiveness of radiotherapy. In the last few years, several studies have highlighted an important link between radioresistance, cancer and microRNAs (miRNAs), an emerging class of endogenous non coding RNAs that control gene expression at post-transcriptional/translational level. MiRNAs may influence carcinogenesis at multiple stages and effectively control tumor radiosensitivity as they affect levels of DNA damage repair, cell cycle checkpoint, apoptosis, radio-related signal transduction pathways and tumor microenvironment-related genes. Since radiation- and multidrug resistances are the characteristic properties of numerous type of tumors, there is increasing interest in establishing a clear association between miRNA expression in tumors and chemo- or radio-sensitivity, with regard to predicting or modulating sensitivity. In the present review, we summarize the emerging evidence of miRNA involvement in the radioresponse of breast tumors and discuss their potential as radiosensitizers.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657319","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}
Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors that are derived from most adult tissue as well as cord blood and placenta. MSCs are defined by their adherent nature, ability to propagate in culture and capacity to differentiate into bone fat and cartilage. However, many studies have shown that MSCs, derived from different tissues, differ both in their in situ and in vitro phenotypes. Despite abundance of MSCs studies, little is known about the molecular events that control their tissue specific nature. Two recent studies comparing MSCs derived from different tissues have now found clues to the molecular mechanisms that control the tissue specific nature ofthese cells. In the first, the superior genomic stability of adipose derived MSCs (ASCs), compared to bone marrow (BM) MSCs, was explained by reduced H19, a long non-coding RNA expression and increased p53 activity of ASCs. In the second, a compression of abdominal and subcutaneous ASCs reveals poor propagation, differentiation and migration capacities of abdominal ASCs that is explained by their increased tendency to over-accumulate reactive oxygen species (ROS) in culture. ROS over production in abdominal ASCs was shown to be controlled by the NADPH oxidase NOX1. The unique features of MSCs derived from different tissues suggest a tissue specific molecular signature arising from the tissue of origin that is retained during culture. The implications of this phenomenon on our understanding of the role and function of MSCs in situ as well as on their clinical utilization, is discussed.
{"title":"The tissue specific nature of mesenchymal stem/stromal cells: gaining better understanding for improved clinical outcomes","authors":"Ofer Shoshani, D. Zipori, N. Shani","doi":"10.14800/RD.780","DOIUrl":"https://doi.org/10.14800/RD.780","url":null,"abstract":"Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors that are derived from most adult tissue as well as cord blood and placenta. MSCs are defined by their adherent nature, ability to propagate in culture and capacity to differentiate into bone fat and cartilage. However, many studies have shown that MSCs, derived from different tissues, differ both in their in situ and in vitro phenotypes. Despite abundance of MSCs studies, little is known about the molecular events that control their tissue specific nature. Two recent studies comparing MSCs derived from different tissues have now found clues to the molecular mechanisms that control the tissue specific nature ofthese cells. In the first, the superior genomic stability of adipose derived MSCs (ASCs), compared to bone marrow (BM) MSCs, was explained by reduced H19, a long non-coding RNA expression and increased p53 activity of ASCs. In the second, a compression of abdominal and subcutaneous ASCs reveals poor propagation, differentiation and migration capacities of abdominal ASCs that is explained by their increased tendency to over-accumulate reactive oxygen species (ROS) in culture. ROS over production in abdominal ASCs was shown to be controlled by the NADPH oxidase NOX1. The unique features of MSCs derived from different tissues suggest a tissue specific molecular signature arising from the tissue of origin that is retained during culture. The implications of this phenomenon on our understanding of the role and function of MSCs in situ as well as on their clinical utilization, is discussed.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657271","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}
Arterial inflammaging highly contributes to cardiovascular morbidity and mortality. As vascular cells age they become senescent and sustain a chronic low grade sterile inflammation by acquiring a senescence-associated secretory phenotype (SASP). The molecular mechanisms leading to the phenotypic changes affecting endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are also relevant for the pathogenesis of vascular diseases, such as atherosclerosis and hypertension. Therefore, unravelling the etiology of vascular inflammaging becomes of crucial importance. MicroRNAs (miRNAs) are small non-coding negative post-transcriptional regulator that are emerging as promising drug targets. MicroRNA-34a (miR-34a) had been implicated in tissues aging and endothelial and endothelial progenitor cells senescence. Our recent work showed that this miRNA is upregulated in aged mouse aortas as well as in senescent VSMCs. Conversely, its target SIRT1 is downregulated in the same specimens. We also found that miR-34a can inhibit VSMCs proliferation and induce VSMCs senescence, the latter by the direct regulation of SIRT1. Notably, for the first time, we demonstrated that miR-34a is also able to modulate the SASP by inducing the transcriptional expression of a subset of pro-inflammatory factors in a SIRT1-independent manner. These data support a model in which the age-dependent upregulation of miR-34a, by affecting senescence and inflammation of vascular cells, could play a causal role to arterial dysfunctions. Hence, further studies are necessary to unravel miR-34a-dependent mechanisms leading to arterial inflammaging in order to develop an effective strategy to age-related cardiovascular complications.
{"title":"MicroRNA-34a: a new player in arterial inflammaging","authors":"I. Badi, A. Raucci","doi":"10.14800/RD.753","DOIUrl":"https://doi.org/10.14800/RD.753","url":null,"abstract":"Arterial inflammaging highly contributes to cardiovascular morbidity and mortality. As vascular cells age they become senescent and sustain a chronic low grade sterile inflammation by acquiring a senescence-associated secretory phenotype (SASP). The molecular mechanisms leading to the phenotypic changes affecting endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are also relevant for the pathogenesis of vascular diseases, such as atherosclerosis and hypertension. Therefore, unravelling the etiology of vascular inflammaging becomes of crucial importance. MicroRNAs (miRNAs) are small non-coding negative post-transcriptional regulator that are emerging as promising drug targets. MicroRNA-34a (miR-34a) had been implicated in tissues aging and endothelial and endothelial progenitor cells senescence. Our recent work showed that this miRNA is upregulated in aged mouse aortas as well as in senescent VSMCs. Conversely, its target SIRT1 is downregulated in the same specimens. We also found that miR-34a can inhibit VSMCs proliferation and induce VSMCs senescence, the latter by the direct regulation of SIRT1. Notably, for the first time, we demonstrated that miR-34a is also able to modulate the SASP by inducing the transcriptional expression of a subset of pro-inflammatory factors in a SIRT1-independent manner. These data support a model in which the age-dependent upregulation of miR-34a, by affecting senescence and inflammation of vascular cells, could play a causal role to arterial dysfunctions. Hence, further studies are necessary to unravel miR-34a-dependent mechanisms leading to arterial inflammaging in order to develop an effective strategy to age-related cardiovascular complications.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657260","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}
SINE retrotransposons of the Alu subfamily are the most numerous active mobile DNA elements in the human genome. Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, but activated in response to viral infection, genotoxic anticancer agents and other stimuli, through uncharacterized epigenetic switches interspersed throughout the genome. The elucidation of Alu RNA roles in cell biology and pathology has long been hampered by difficulties in their profiling at single-locus resolution, due to their repetitive nature. We recently found how to overcome this limitation by computational screening of RNA-seq data, thus opening the way to Alu transcriptome profiling as a novel tool to explore disease-related epigenome alterations.
{"title":"Alu expression profiles as a novel RNA signature in biology and disease","authors":"D. Carnevali, G. Dieci","doi":"10.14800/RD.735","DOIUrl":"https://doi.org/10.14800/RD.735","url":null,"abstract":"SINE retrotransposons of the Alu subfamily are the most numerous active mobile DNA elements in the human genome. Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, but activated in response to viral infection, genotoxic anticancer agents and other stimuli, through uncharacterized epigenetic switches interspersed throughout the genome. The elucidation of Alu RNA roles in cell biology and pathology has long been hampered by difficulties in their profiling at single-locus resolution, due to their repetitive nature. We recently found how to overcome this limitation by computational screening of RNA-seq data, thus opening the way to Alu transcriptome profiling as a novel tool to explore disease-related epigenome alterations.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657725","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}
Control over the delivery of different functionalities and their synchronized activation in vivo is a challenging undertaking that requires careful design and implementation. The goal of the research highlighted herein was to develop a platform allowing the simultaneous activation of multiple RNA interference pathways and other functionalities inside cells. Our team has developed several RNA, RNA/DNA and DNA/RNA nanoparticles able to successfully complete such tasks. The reported designs can potentially be used to target myriad of different diseases.
{"title":"RNA and DNA nanoparticles for triggering RNA interference.","authors":"Ziad El Tannir, K. Afonin, B. Shapiro","doi":"10.14800/RD.724","DOIUrl":"https://doi.org/10.14800/RD.724","url":null,"abstract":"Control over the delivery of different functionalities and their synchronized activation in vivo is a challenging undertaking that requires careful design and implementation. The goal of the research highlighted herein was to develop a platform allowing the simultaneous activation of multiple RNA interference pathways and other functionalities inside cells. Our team has developed several RNA, RNA/DNA and DNA/RNA nanoparticles able to successfully complete such tasks. The reported designs can potentially be used to target myriad of different diseases.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 Suppl 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657659","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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