Pub Date : 2016-01-01Epub Date: 2016-06-06DOI: 10.14800/rd.1336
Jorge Cruz-Reyes, Blaine H M Mooers, Zakaria Abu-Adas, Vikas Kumar, Shelly Gulati
Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100-400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans.
{"title":"DEAH-RHA helicase•Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes.","authors":"Jorge Cruz-Reyes, Blaine H M Mooers, Zakaria Abu-Adas, Vikas Kumar, Shelly Gulati","doi":"10.14800/rd.1336","DOIUrl":"https://doi.org/10.14800/rd.1336","url":null,"abstract":"<p><p>Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100-400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34319886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CCDC26 on chromosome 8q24 is considered to encode a long intergenic noncoding RNA because the short open reading frame within the mRNA transcribed from this gene is not conserved in any other species. Genome-wide analysis has revealed association of CCDC26 with certain tumors, for instance low-level glioma. Moreover, 1.5- to 2-fold amplifications of the whole or part of the CCDC26 genetic locus have been observed in pediatric acute myeloid leukemia patients. The CCDC26 gene is amplified in the HL-60 acute myeloid leukemia cell line, in which double minute chromosomes—abnormal tiny chromosomes—harbor the CCDC26 gene. We examined the function of CCDC26 by gene knock-down (KD) using short hairpin RNAs in K562 human myeloid leukemia cells. In four stable KD clones, CCDC26 expression was suppressed to 1% of its normal level by transcriptional gene suppression, not post-transcriptional suppression. The growth rates of these KD clones were reduced compared with those of control cells in media containing high serum concentrations. In contrast, in media containing much lower serum concentrations, the KD clones exhibited significantly higher growth rates than controls, and increased survival after serum withdrawal. Enhanced expression of a receptor tyrosine kinase, KIT , was detected in the KD clones, and treatment with ISCK03, a KIT inhibitor, eliminated their increased survival in the absence of serum. Therefore, CCDC26 seems to control myeloid leukemia cell growth through regulation of KIT expression. These observations suggest that CCDC26 is a tumor-suppressive long noncoding RNA because it suppresses the KIT oncogene that supports survival of cancer cells in the stem cell state.
{"title":"The role of the CCDC26 long noncoding RNA as a tumor suppressor","authors":"T. Hirano","doi":"10.14800/RD.1022","DOIUrl":"https://doi.org/10.14800/RD.1022","url":null,"abstract":"CCDC26 on chromosome 8q24 is considered to encode a long intergenic noncoding RNA because the short open reading frame within the mRNA transcribed from this gene is not conserved in any other species. Genome-wide analysis has revealed association of CCDC26 with certain tumors, for instance low-level glioma. Moreover, 1.5- to 2-fold amplifications of the whole or part of the CCDC26 genetic locus have been observed in pediatric acute myeloid leukemia patients. The CCDC26 gene is amplified in the HL-60 acute myeloid leukemia cell line, in which double minute chromosomes—abnormal tiny chromosomes—harbor the CCDC26 gene. We examined the function of CCDC26 by gene knock-down (KD) using short hairpin RNAs in K562 human myeloid leukemia cells. In four stable KD clones, CCDC26 expression was suppressed to 1% of its normal level by transcriptional gene suppression, not post-transcriptional suppression. The growth rates of these KD clones were reduced compared with those of control cells in media containing high serum concentrations. In contrast, in media containing much lower serum concentrations, the KD clones exhibited significantly higher growth rates than controls, and increased survival after serum withdrawal. Enhanced expression of a receptor tyrosine kinase, KIT , was detected in the KD clones, and treatment with ISCK03, a KIT inhibitor, eliminated their increased survival in the absence of serum. Therefore, CCDC26 seems to control myeloid leukemia cell growth through regulation of KIT expression. These observations suggest that CCDC26 is a tumor-suppressive long noncoding RNA because it suppresses the KIT oncogene that supports survival of cancer cells in the stem cell state.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656842","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}
Splicing is a processs to remove introns from precursor of mRNAs (pre-mRNAs). Introns are excised as a lariat form, and they should be debranched before degradation. This reaction is conferred by a RNA lariat debranching enzyme 1 (Dbr1) protein. The Dbr1 protein is evolutionarily conserved among many species and shares GNHE motif for debranching activity that is identical to protein phosphatase activity center. The human Dbr1 protein has a bipartite type nuclear localization signal, and it shuttles between the nucleus and the cytoplasm, suggesting novel function(s) in the cytoplasm. The human Dbr1 protein interacts with two proteins, Xab2 and hDrn1. Since Xab2 is involved in not only splicing but also transcription-coupled DNA repair (TCR), hDbr1 may also have a role in TCR. Although the function of hDrn1 is not known yet, this protein specifically interact with carboxy terminal of hDbr1 and it is also a nucleo-cytoplasmic shuttling protein. A heterodimer of hDbr1-hDrn1 may have role(s) in both in the nucleus and the cytoplasm of human cells.
{"title":"Human RNA lariat debranching enzyme protein 1 – A surveillant for branch RNAs for degradation","authors":"N. Kataoka","doi":"10.14800/RD.963","DOIUrl":"https://doi.org/10.14800/RD.963","url":null,"abstract":"Splicing is a processs to remove introns from precursor of mRNAs (pre-mRNAs). Introns are excised as a lariat form, and they should be debranched before degradation. This reaction is conferred by a RNA lariat debranching enzyme 1 (Dbr1) protein. The Dbr1 protein is evolutionarily conserved among many species and shares GNHE motif for debranching activity that is identical to protein phosphatase activity center. The human Dbr1 protein has a bipartite type nuclear localization signal, and it shuttles between the nucleus and the cytoplasm, suggesting novel function(s) in the cytoplasm. The human Dbr1 protein interacts with two proteins, Xab2 and hDrn1. Since Xab2 is involved in not only splicing but also transcription-coupled DNA repair (TCR), hDbr1 may also have a role in TCR. Although the function of hDrn1 is not known yet, this protein specifically interact with carboxy terminal of hDbr1 and it is also a nucleo-cytoplasmic shuttling protein. A heterodimer of hDbr1-hDrn1 may have role(s) in both in the nucleus and the cytoplasm of human cells.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657785","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}
G. Sommer, Avery W. Zierk, A. Fedarovich, Alexander Brock, Dzmitry Fedarovich, T. Heise
Single-stranded RNA molecules fold intensively into secondary and tertiary structures and are often trapped in non-functional configurations. To adapt a functional configuration, structural changes have to be achieved. RNA helicases and RNA chaperones are proteins able to assist those structural rearrangements in an ATP-dependent or ATP-independent manner, respectively. The cancer-associated RNA-binding protein La (LARP3) is an RNA chaperone involved in various aspects of the RNA metabolism. Recently the RNA chaperone domain within the human La protein has been mapped and demonstrated that its activity is required to stimulate cyclin D1-internal ribosome entry site (IRES)-dependent protein synthesis. Furthermore, it has been shown that the La protein can be phosphorylated by serine/threonine kinase AKT in vitro . Taken together, we suggest a model in which the RNA chaperone La stimulates translation of specific target mRNAs by assisting structural changes in their translation start site surrounding RNA region.
{"title":"The RNA chaperon activity of the human La protein (LARP3)","authors":"G. Sommer, Avery W. Zierk, A. Fedarovich, Alexander Brock, Dzmitry Fedarovich, T. Heise","doi":"10.14800/RD.872","DOIUrl":"https://doi.org/10.14800/RD.872","url":null,"abstract":"Single-stranded RNA molecules fold intensively into secondary and tertiary structures and are often trapped in non-functional configurations. To adapt a functional configuration, structural changes have to be achieved. RNA helicases and RNA chaperones are proteins able to assist those structural rearrangements in an ATP-dependent or ATP-independent manner, respectively. The cancer-associated RNA-binding protein La (LARP3) is an RNA chaperone involved in various aspects of the RNA metabolism. Recently the RNA chaperone domain within the human La protein has been mapped and demonstrated that its activity is required to stimulate cyclin D1-internal ribosome entry site (IRES)-dependent protein synthesis. Furthermore, it has been shown that the La protein can be phosphorylated by serine/threonine kinase AKT in vitro . Taken together, we suggest a model in which the RNA chaperone La stimulates translation of specific target mRNAs by assisting structural changes in their translation start site surrounding RNA region.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658179","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}
Wang Dan, Zeng Qinghai, Lu Jianyun, Chen Jing, Yang Shengbo, Xia Fang, D. Shu, Deng Qiancheng, Yang Yan, Huang Jinhua
Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules with poor protein coding potential and are usually larger than 200 nucleotides. SPRY4-IT1, a member of lncRNA, is derived from an intronic region within the SPRY4 gene. And accumulating evidence demonstrates that aberrant expression of SPRY4-IT1 is involved in the development of various diseases such as melanoma, esophageal squamous cell carcinoma (ESCC), renal cancer, gastric cancer, breast cancer, bladder cancer, Non-small-cell lung cancer (NSCLC), and preeclampsia. SPRY4-IT1 is significantly related to not only progression and prognosis of diseases but also cell proliferation, migration, invasion. SPRY4-IT1 contributes to various diseases via different molecular mechanism such as regulating the expression of proteins related to cell growth and migration, involving in epithelial–mesenchymal transition (EMT), affecting lipid metabolism, and regulating downstream gene expression. Moreover, SPRY4-IT1 can also be regulated by some epigenetic factors including Zeste homolog 2 (EZH2). Therefore, SPRY4-IT1 may be a novel prognostic biomarker and a potential therapeutic candidate for different diseases including various solid cancers and preeclampsia.
{"title":"Long non-coding RNA SPRY4-IT1: a new player in different diseases","authors":"Wang Dan, Zeng Qinghai, Lu Jianyun, Chen Jing, Yang Shengbo, Xia Fang, D. Shu, Deng Qiancheng, Yang Yan, Huang Jinhua","doi":"10.14800/RD.916","DOIUrl":"https://doi.org/10.14800/RD.916","url":null,"abstract":"Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules with poor protein coding potential and are usually larger than 200 nucleotides. SPRY4-IT1, a member of lncRNA, is derived from an intronic region within the SPRY4 gene. And accumulating evidence demonstrates that aberrant expression of SPRY4-IT1 is involved in the development of various diseases such as melanoma, esophageal squamous cell carcinoma (ESCC), renal cancer, gastric cancer, breast cancer, bladder cancer, Non-small-cell lung cancer (NSCLC), and preeclampsia. SPRY4-IT1 is significantly related to not only progression and prognosis of diseases but also cell proliferation, migration, invasion. SPRY4-IT1 contributes to various diseases via different molecular mechanism such as regulating the expression of proteins related to cell growth and migration, involving in epithelial–mesenchymal transition (EMT), affecting lipid metabolism, and regulating downstream gene expression. Moreover, SPRY4-IT1 can also be regulated by some epigenetic factors including Zeste homolog 2 (EZH2). Therefore, SPRY4-IT1 may be a novel prognostic biomarker and a potential therapeutic candidate for different diseases including various solid cancers and preeclampsia.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657749","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}
Although synthetic small interfering RNA (siRNA) has been extensively used to downregulate any protein-coding mRNA, several key issues still remain unsolved. The acyclic threoninol nucleic acid (aTNA), placed at certain siRNA positions, is a useful modification to reduce the oligonucleotides vulnerability towards nucleases. In addition, it can be exploited to avoid several OFF-target effects that limit the biological safety of the RNAi-based agents.
{"title":"RNA modified with acyclic threoninol nucleic acids for RNA interference","authors":"A. Alagia, M. Terrazas, R. Eritja","doi":"10.14800/RD.907","DOIUrl":"https://doi.org/10.14800/RD.907","url":null,"abstract":"Although synthetic small interfering RNA (siRNA) has been extensively used to downregulate any protein-coding mRNA, several key issues still remain unsolved. The acyclic threoninol nucleic acid (aTNA), placed at certain siRNA positions, is a useful modification to reduce the oligonucleotides vulnerability towards nucleases. In addition, it can be exploited to avoid several OFF-target effects that limit the biological safety of the RNAi-based agents.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657738","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}
Pluripotent embryonic stem cells (ESCs) and cancer cells share traits and molecular mechanisms, such as the ability to self-renew and a block in cellular differentiation. Both ESCs and tumor cells have a large proliferative capacity and cellular plasticity. One common denominator linking these two cell types is the BET family member, BRD4. BRD4 plays a critical role in gene regulation, recruiting the active form of Positive Elongation Factor b (P-TEFb) to RNA polymerase II at paused promoters ultimately resulting in the production of elongated mRNAs. BRD4 is deregulated in many cancers making it an attractive therapeutic target. Here, we highlight the recent findings coupling the role of BRD4 in pluripotency and tumorigenesis.
{"title":"The converging roles of BRD4 and gene transcription in pluripotency and oncogenesis.","authors":"Tao Wu, M. Donohoe","doi":"10.14800/RD.894","DOIUrl":"https://doi.org/10.14800/RD.894","url":null,"abstract":"Pluripotent embryonic stem cells (ESCs) and cancer cells share traits and molecular mechanisms, such as the ability to self-renew and a block in cellular differentiation. Both ESCs and tumor cells have a large proliferative capacity and cellular plasticity. One common denominator linking these two cell types is the BET family member, BRD4. BRD4 plays a critical role in gene regulation, recruiting the active form of Positive Elongation Factor b (P-TEFb) to RNA polymerase II at paused promoters ultimately resulting in the production of elongated mRNAs. BRD4 is deregulated in many cancers making it an attractive therapeutic target. Here, we highlight the recent findings coupling the role of BRD4 in pluripotency and tumorigenesis.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658191","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}
{"title":"The converging roles of BRD4 and gene transcription in pluripotency and oncogenesis.","authors":"Tao Wu, Mary E Donohoe","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578175/pdf/nihms717908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34102474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob Masika, Ya-Nan Zhao, J. Hescheler, Hua-min Liang
Accumulating lines of evidence have revealed that microRNAs (miRNAs) play critical roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation. They act either as tumour suppressors or oncogenes, and alteration in their expression patterns has been linked to onset, progression and chemoresistance of various cancers. Moreover, miRNAs are also crucial for the regulation of cancer stem cells (CSCs) self-renewal and proliferation as well as control of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Several experimental and epidemiologic studies have shown that dietary intake of natural agents such as baicalin, ginsenoside, curcumin, resveratrol, genistein, epigallocatechin-3-gallate (EGCG), indole-3-carbinol, 3,3΄-diindolylmethane (DIM) including antioxidants among others is inversely associated with the risk for cancer, demonstrating the inhibitory effects of natural agents on carcinogenesis. Moreover, the anticancer agents from natural plants have been found to inhibit the development and progression of cancer through the regulation of cellular signaling pathways. Importantly, natural agents also up-regulate the expression of tumor-suppressive miRNAs and down-regulate the expression of oncogenic miRNAs, leading to the inhibition of cancer cell growth and cancer stem cell self-renewal through modulation of cellular signaling network. Furthermore, natural agents also regulate epigenetically deregulated DNAs and miRNAs, leading to the normalization of altered cellular signaling in cancer cells. Therefore, natural agents could have much broader use in the prevention and/or treatment of various types of cancer in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are needed to realize the true value of natural agents in the prevention and/or treatment of cancer. Herein, we provide an overview of natural agents’ modulation of miRNA expression as well as highlight the significance of these observations as potential new strategies in cancer therapies. This review will help us to know in detail how miRNAs are regulated by natural agents and also help to develop more effective and secure natural agents for clinical therapies.
{"title":"Modulation of miRNAs by natural agents: Nature’s way of dealing with cancer","authors":"Jacob Masika, Ya-Nan Zhao, J. Hescheler, Hua-min Liang","doi":"10.14800/RD.861","DOIUrl":"https://doi.org/10.14800/RD.861","url":null,"abstract":"Accumulating lines of evidence have revealed that microRNAs (miRNAs) play critical roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation. They act either as tumour suppressors or oncogenes, and alteration in their expression patterns has been linked to onset, progression and chemoresistance of various cancers. Moreover, miRNAs are also crucial for the regulation of cancer stem cells (CSCs) self-renewal and proliferation as well as control of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Several experimental and epidemiologic studies have shown that dietary intake of natural agents such as baicalin, ginsenoside, curcumin, resveratrol, genistein, epigallocatechin-3-gallate (EGCG), indole-3-carbinol, 3,3΄-diindolylmethane (DIM) including antioxidants among others is inversely associated with the risk for cancer, demonstrating the inhibitory effects of natural agents on carcinogenesis. Moreover, the anticancer agents from natural plants have been found to inhibit the development and progression of cancer through the regulation of cellular signaling pathways. Importantly, natural agents also up-regulate the expression of tumor-suppressive miRNAs and down-regulate the expression of oncogenic miRNAs, leading to the inhibition of cancer cell growth and cancer stem cell self-renewal through modulation of cellular signaling network. Furthermore, natural agents also regulate epigenetically deregulated DNAs and miRNAs, leading to the normalization of altered cellular signaling in cancer cells. Therefore, natural agents could have much broader use in the prevention and/or treatment of various types of cancer in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are needed to realize the true value of natural agents in the prevention and/or treatment of cancer. Herein, we provide an overview of natural agents’ modulation of miRNA expression as well as highlight the significance of these observations as potential new strategies in cancer therapies. This review will help us to know in detail how miRNAs are regulated by natural agents and also help to develop more effective and secure natural agents for clinical therapies.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658118","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}
Cellular senescence is a stable cell cycle arrest that inhibits the outgrowth of pre-cancerous cells but is also implicated in wound healing, embryonic development, aging and age-related pathologies. Our knowledge on gene regulatory circuits that establish and maintain the senescence phenotype is highly fragmentary. Here, we provide several lines of evidence supporting a critical and novel function of scaffolding-attachment-factor A SAF-A and long, noncoding RNA PANDA in the establishment and maintenance of the senescence phenotype. First, we demonstrate that SAF-A and PANDA are differentially expressed in presenescent compared to senescent cells. Second, we show that both SAF-A and PANDA actively contribute to senescence induction and maintenance. Finally, we establish that SAF-A and PANDA physically and functionally interact to directly repress senescence- and proliferation-promoting genes by regulating access of polycomb repressive complexes PRC1 and PRC2 as well as transcription factor NF-YA to their cognate target genes. Together, our data identify DNA-RNA-binding protein SAF-A and long, noncoding RNA PANDA as key actors in senescence cell fate decision and unravel the importance of cell fate dependent target gene changes of transcription factors and noncoding RNAs.
{"title":"It takes four to tango: Long noncoding RNA PANDA, SAF-A, polycomb repressive complexes and NF-Y in senescence regulation","authors":"O. Bischof, P. Puvvula","doi":"10.14800/RD.855","DOIUrl":"https://doi.org/10.14800/RD.855","url":null,"abstract":"Cellular senescence is a stable cell cycle arrest that inhibits the outgrowth of pre-cancerous cells but is also implicated in wound healing, embryonic development, aging and age-related pathologies. Our knowledge on gene regulatory circuits that establish and maintain the senescence phenotype is highly fragmentary. Here, we provide several lines of evidence supporting a critical and novel function of scaffolding-attachment-factor A SAF-A and long, noncoding RNA PANDA in the establishment and maintenance of the senescence phenotype. First, we demonstrate that SAF-A and PANDA are differentially expressed in presenescent compared to senescent cells. Second, we show that both SAF-A and PANDA actively contribute to senescence induction and maintenance. Finally, we establish that SAF-A and PANDA physically and functionally interact to directly repress senescence- and proliferation-promoting genes by regulating access of polycomb repressive complexes PRC1 and PRC2 as well as transcription factor NF-YA to their cognate target genes. Together, our data identify DNA-RNA-binding protein SAF-A and long, noncoding RNA PANDA as key actors in senescence cell fate decision and unravel the importance of cell fate dependent target gene changes of transcription factors and noncoding RNAs.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658041","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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