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[PMID]:29324880
[Au] Autor:Zhao K; Zheng WW; Dong XM; Yin RH; Gao R; Li X; Liu JF; Zhan YQ; Yu M; Chen H; Ge CH; Ning HM; Yang XM; Li CY
[Ad] Endereço:State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
[Ti] Título:EDAG promotes the expansion and survival of human CD34+ cells.
[So] Source:PLoS One;13(1):e0190794, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:EDAG is multifunctional transcriptional regulator primarily expressed in the linloc-kit+Sca-1+ hematopoietic stem cells (HSC) and CD34+ progenitor cells. Previous studies indicate that EDAG is required for maintaining hematopoietic lineage commitment balance. Here using ex vivo culture and HSC transplantation models, we report that EDAG enhances the proliferative potential of human cord blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their repopulating capacity. Moreover, EDAG overexpression induces rapid entry of CD34+ cells into the cell cycle. Gene expression profile analysis indicate that EDAG knockdown leads to down-regulation of various positive cell cycle regulators including cyclin A, B, D, and E. Together these data provides novel insights into EDAG in regulation of expansion and survival of human hematopoietic stem/progenitor cells.
[Mh] Termos MeSH primário: Antígenos CD34/metabolismo
Proliferação Celular/fisiologia
Sobrevivência Celular/fisiologia
Sangue Fetal/metabolismo
Células-Tronco Hematopoéticas/metabolismo
Proteínas Nucleares/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Ciclo Celular/fisiologia
Células Cultivadas
Transplante de Células-Tronco de Sangue do Cordão Umbilical
Ciclinas/metabolismo
Feminino
Sangue Fetal/citologia
Células-Tronco Hematopoéticas/química
Seres Humanos
Subunidade gama Comum de Receptores de Interleucina/deficiência
Subunidade gama Comum de Receptores de Interleucina/genética
Camundongos Endogâmicos NOD
Camundongos Knockout
Camundongos SCID
Proteínas Nucleares/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Cyclins); 0 (HEMGN protein, human); 0 (Il2rg protein, mouse); 0 (Interleukin Receptor Common gamma Subunit); 0 (Nuclear Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190794


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[PMID]:27773672
[Au] Autor:Dankert JF; Rona G; Clijsters L; Geter P; Skaar JR; Bermudez-Hernandez K; Sassani E; Fenyö D; Ueberheide B; Schneider R; Pagano M
[Ad] Endereço:Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; Perlmutter NYU Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA.
[Ti] Título:Cyclin F-Mediated Degradation of SLBP Limits H2A.X Accumulation and Apoptosis upon Genotoxic Stress in G2.
[So] Source:Mol Cell;64(3):507-519, 2016 Nov 03.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A.X (encoded by H2AFX). Upon genotoxic stress in G2, high levels of H2A.X lead to persistent γH2A.X signaling, high levels of H2A.X phosphorylated on Tyr142, high levels of p53, and induction of apoptosis. We propose that cyclin F co-evolved with the appearance of stem-loops in vertebrate H2AFX mRNA to mediate SLBP degradation, thereby limiting H2A.X synthesis and cell death upon genotoxic stress.
[Mh] Termos MeSH primário: Ciclinas/genética
Dano ao DNA
Pontos de Checagem da Fase G2 do Ciclo Celular/genética
Histonas/genética
Proteínas Nucleares/genética
RNA Mensageiro/genética
Fatores de Poliadenilação e Clivagem de mRNA/genética
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Apoptose
Sítios de Ligação
Linhagem Celular Tumoral
Ciclinas/metabolismo
Regulação da Expressão Gênica
Células HEK293
Células HeLa
Histonas/metabolismo
Seres Humanos
Camundongos
Proteínas Nucleares/metabolismo
Fosforilação
Polirribossomos/genética
Polirribossomos/metabolismo
Ligação Proteica
Proteólise
RNA Mensageiro/metabolismo
Ratos
Transdução de Sinais
Xenopus laevis
Peixe-Zebra
Fatores de Poliadenilação e Clivagem de mRNA/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCNF protein, human); 0 (Cyclins); 0 (H2AFX protein, human); 0 (Histones); 0 (Nuclear Proteins); 0 (RNA, Messenger); 0 (SLBP protein, human); 0 (mRNA Cleavage and Polyadenylation Factors)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180119
[Lr] Data última revisão:
180119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


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[PMID]:29261770
[Au] Autor:Wang B; Liu D; Wang C; Wang Q; Zhang H; Liu G; He Q; Zhang L
[Ad] Endereço:Marine Bio-pharmaceutical Institute, Second Military Medical University, Shanghai, China.
[Ti] Título:Tentacle extract from the jellyfish Cyanea capillata increases proliferation and migration of human umbilical vein endothelial cells through the ERK1/2 signaling pathway.
[So] Source:PLoS One;12(12):e0189920, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Wound healing is a complex biological process, and current research finds that jellyfish have a great capacity for promoting growth and healing. However, the underlying mechanisms remain unclear. Thus, this study was conducted to investigate the molecular mechanisms and effects of a tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) on cell proliferation and migration in human umbilical vein endothelial cells (HUVECs). First, our results showed that TE at the concentration of 1 µg/ml could promote cell proliferation over various durations, induce a transition of the cells from the G1-phase to the S/G2-phase of the cell cycle, and increase the expression of cell cycle proteins (CyclinB1 and CyclinD1). Second, we found that TE could activate the PI3K/Akt, ERK1/2 and JNK MAPK signaling pathways but not the NF-κB signaling pathway or the apoptosis signaling cascade. Finally, we demonstrated that the TE-induced expression of cell cycle proteins was decreased by ERK1/2 inhibitor PD98059 but not by PI3K inhibitor LY294002 or JNK inhibitor SP600125. Similarly, the TE-enhanced migration ability of HUVECs was also markedly attenuated by PD98059. Taken together, our findings indicate that TE-induced proliferation and migration in HUVECs mainly occurred through the ERK1/2 MAPK signaling pathway. These results are instructively important for further research on the isolation and purification of growth-promoting factors from C. capillata and are hopeful as a means to improve human wound repair in unfavorable conditions.
[Mh] Termos MeSH primário: Estruturas Animais/química
Movimento Celular/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana/citologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Cifozoários/anatomia & histologia
Extratos de Tecidos/farmacologia
[Mh] Termos MeSH secundário: Animais
Ciclo Celular/efeitos dos fármacos
Proteínas de Ciclo Celular/metabolismo
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Ciclinas/metabolismo
Imunofluorescência
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana/metabolismo
Seres Humanos
NF-kappa B/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Cyclins); 0 (NF-kappa B); 0 (Protein Kinase Inhibitors); 0 (Tissue Extracts); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189920


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[PMID]:27771213
[Au] Autor:Søndergaard RH; Follin B; Lund LD; Juhl M; Ekblond A; Kastrup J; Haack-Sørensen M
[Ad] Endereço:Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
[Ti] Título:Senescence and quiescence in adipose-derived stromal cells: Effects of human platelet lysate, fetal bovine serum and hypoxia.
[So] Source:Cytotherapy;19(1):95-106, 2017 01.
[Is] ISSN:1477-2566
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AIMS: Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent. METHODS: ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and ß-galactosidase activity. RESULTS: hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions. CONCLUSION: Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions.
[Mh] Termos MeSH primário: Tecido Adiposo/citologia
Plaquetas/química
Técnicas de Cultura de Células/métodos
Células Estromais/citologia
[Mh] Termos MeSH secundário: Adulto
Animais
Bovinos
Ciclo Celular
Hipóxia Celular
Proliferação Celular
Células Cultivadas
Senescência Celular
Ciclinas/genética
Ciclinas/metabolismo
Feminino
Regulação da Expressão Gênica
Seres Humanos
Imunofenotipagem
Masculino
Soro
Células Estromais/fisiologia
beta-Galactosidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cyclins); EC 3.2.1.23 (beta-Galactosidase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171207
[Lr] Data última revisão:
171207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28946006
[Au] Autor:Iwahori S; Kalejta RF
[Ad] Endereço:Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, United States.
[Ti] Título:Phosphorylation of transcriptional regulators in the retinoblastoma protein pathway by UL97, the viral cyclin-dependent kinase encoded by human cytomegalovirus.
[So] Source:Virology;512:95-103, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human cytomegalovirus (HCMV) encodes a viral cyclin-dependent kinase (v-CDK), the UL97 protein. UL97 phosphorylates Rb, p107 and p130, thereby inactivating all three retinoblastoma (Rb) family members. Rb proteins function through regulating the activity of transcription factors to which they bind. Therefore, we examined whether the UL97-mediated regulation of the Rb tumor suppressors also extended to their binding partners. We observed that UL97 phosphorylates LIN52, a component of p107- and p130-assembled transcriptionally repressive DREAM complexes that control transcription during the G0/G1 phases, and the Rb-associated E2F3 protein that activates transcription through G1 and S phases. Intriguingly, we also identified FoxM1B, a transcriptional regulator during the S and G2 phases, as a UL97 substrate. This survey extends the influence of UL97 beyond simply the Rb proteins themselves to their binding partners, as well as past the G1/S transition into later stages of the cell cycle.
[Mh] Termos MeSH primário: Citomegalovirus/enzimologia
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
Proteína do Retinoblastoma/metabolismo
[Mh] Termos MeSH secundário: Células Cultivadas
Ciclinas/genética
Ciclinas/metabolismo
Citomegalovirus/metabolismo
Fator de Transcrição E2F3/genética
Fator de Transcrição E2F3/metabolismo
Proteína Forkhead Box M1/genética
Proteína Forkhead Box M1/metabolismo
Fase G1
Regulação Viral da Expressão Gênica/fisiologia
Seres Humanos
Proteínas Interatuantes com Canais de Kv/genética
Proteínas Interatuantes com Canais de Kv/metabolismo
Mutagênese Sítio-Dirigida
Fosforilação
Fosfotransferases (Aceptor do Grupo Álcool)/genética
Subunidades Proteicas
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Fase de Repouso do Ciclo Celular
Proteína do Retinoblastoma/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (E2F3 Transcription Factor); 0 (FOXM1 protein, human); 0 (Forkhead Box Protein M1); 0 (KCNIP3 protein, human); 0 (Kv Channel-Interacting Proteins); 0 (Protein Subunits); 0 (Repressor Proteins); 0 (Retinoblastoma Protein); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.- (ganciclovir kinase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:28938001
[Au] Autor:Chandra U; Yadav A; Kumar D; Saha S
[Ad] Endereço:Department of Microbiology, University of Delhi South Campus, New Delhi, India.
[Ti] Título:Cell cycle stage-specific transcriptional activation of cyclins mediated by HAT2-dependent H4K10 acetylation of promoters in Leishmania donovani.
[So] Source:PLoS Pathog;13(9):e1006615, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromatin modifications affect several processes. In investigating the Leishmania donovani histone acetyltransferase HAT2, using in vitro biochemical assays and HAT2-heterozygous genomic knockout we found the constitutively nuclear HAT2 acetylated histone H4K10 in vitro and in vivo. HAT2 was essential. HAT2-depleted cells displayed growth and cell cycle defects, and poor survival in host cells. Real time PCR and DNA microarray analyses, as well as rescue experiments, revealed that downregulation of cyclins CYC4 and CYC9 were responsible for S phase and G2/M defects of HAT2-depleted cells respectively. Leishmania genes are arranged in unidirectional clusters, and clustered genes are coordinately transcribed as long polycistronic units, typically from divergent strand switch regions (dSSRs) which initiate transcription bidirectionally on opposite strands. In investigating the mechanism by which CYC4 and CYC9 expression levels are reduced in HAT2-depleted cells without other genes in their polycistronic transcription units being coordinately downregulated, we found using reporter assays that CYC4 and CYC9 have their own specific promoters. Chromatin immunoprecipitation assays with H4acetylK10 antibodies and real time PCR analyses of RNA suggested these gene-specific promoters were activated in cell cycle-dependent manner. Nuclear run-on analyses confirmed that CYC4 and CYC9 were transcriptionally activated from their own promoters at specific cell cycle stages. Thus, there are two tiers of gene regulation. Transcription of polycistronic units primarily initiates at dSSRs, and this most likely occurs constitutively. A subset of genes have their own promoters, at least some of which are activated in a cell-cycle dependent manner. This second tier of regulation is more sensitive to H4K10 acetylation levels, resulting in downregulation of expression in HAT2-depleted cells. This report presents the first data pointing to cell cycle-specific activation of promoters in trypanosomatids, thus uncovering new facets of gene regulation in this parasite family.
[Mh] Termos MeSH primário: Ciclinas/genética
Genes de Protozoários/genética
Histonas/genética
Leishmania donovani/genética
Proteínas de Protozoários/genética
[Mh] Termos MeSH secundário: Acetilação
Imunoprecipitação da Cromatina
Regulação da Expressão Gênica
Leishmania donovani/metabolismo
Análise de Sequência com Séries de Oligonucleotídeos
Regiões Promotoras Genéticas
Proteínas de Protozoários/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (Histones); 0 (Protozoan Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006615


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[PMID]:28873438
[Au] Autor:Musacchia F; Vasilev F; Borra M; Biffali E; Sanges R; Santella L; Chun JT
[Ad] Endereço:Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Napoli, Italy.
[Ti] Título:De novo assembly of a transcriptome from the eggs and early embryos of Astropecten aranciacus.
[So] Source:PLoS One;12(9):e0184090, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Starfish have been instrumental in many fields of biological and ecological research. Oocytes of Astropecten aranciacus, a common species native to the Mediterranean Sea and the East Atlantic, have long been used as an experimental model to study meiotic maturation, fertilization, intracellular Ca2+ signaling, and cell cycle controls. However, investigation of the underlying molecular mechanisms has often been hampered by the overall lack of DNA or protein sequences for the species. In this study, we have assembled a transcriptome for this species from the oocytes, eggs, zygotes, and early embryos, which are known to have the highest RNA sequence complexity. Annotation of the transcriptome identified over 32,000 transcripts including the ones that encode 13 distinct cyclins and as many cyclin-dependent kinases (CDK), as well as the expected components of intracellular Ca2+ signaling toolkit. Although the mRNAs of cyclin and CDK families did not undergo significant abundance changes through the stages from oocyte to early embryo, as judged by real-time PCR, the transcript encoding Mos, a negative regulator of mitotic cell cycle, was drastically reduced during the period of rapid cleavages. Molecular phylogenetic analysis using the homologous amino acid sequences of cytochrome oxidase subunit I from A. aranciacus and 30 other starfish species indicated that Paxillosida, to which A. aranciacus belongs, is not likely to be the most basal order in Asteroidea. Taken together, the first transcriptome we assembled in this species is expected to enable us to perform comparative studies and to design gene-specific molecular tools with which to tackle long-standing biological questions.
[Mh] Termos MeSH primário: Embrião não Mamífero/metabolismo
Óvulo/metabolismo
Estrelas-do-Mar/genética
Estrelas-do-Mar/metabolismo
Transcriptoma/genética
[Mh] Termos MeSH secundário: Animais
Sinalização do Cálcio/genética
Quinases Ciclina-Dependentes/metabolismo
Ciclinas/metabolismo
Bases de Dados de Ácidos Nucleicos
Complexo IV da Cadeia de Transporte de Elétrons/química
Complexo IV da Cadeia de Transporte de Elétrons/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento
Ontologia Genética
Anotação de Sequência Molecular
Filogenia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (RNA, Messenger); EC 1.9.3.1 (Electron Transport Complex IV); EC 2.7.11.22 (Cyclin-Dependent Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184090


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[PMID]:28855110
[Au] Autor:Qiao L; Liu X; Tang Y; Zhao Z; Zhang J; Feng Y
[Ad] Endereço:Department of Colorectal and Hernia Minimally Invasive Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
[Ti] Título:Down regulation of the long non-coding RNA PCAT-1 induced growth arrest and apoptosis of colorectal cancer cells.
[So] Source:Life Sci;188:37-44, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: The long non-coding RNA (lncRNA) was reported to be involved in the progress of various cancers, however, its effect in colorectal cancer (CRC) remains unknown. The goal of the present study is to investigate the function role of lncRNA PCAT-1 in colorectal cancer. MAIN METHODS: The expression of lncRNA PCAT-1 in four CRC cell lines was measured by real-time PCR, and two lncRNA PCAT-1 high expression cell lines were selected. LncRNA PCAT-1 in these two CRC cell lines was down-regulated by shRNA, and the stable transfected cells were established. Functional involvement of lncRNA PCAT-1 in proliferation and apoptosis of the two CRC cells were evaluated in vitro. Mover, the effect of lncRNA PCAT-1 in tumor proliferation was also evaluated in CRC cell xenograft. KEY FINDINGS: The results showed that down-regulation of lncRNA PCAT-1 in CRC cells inhibited proliferation, blocked cell cycle transition, and suppressed the expression of cyclins and c-myc. The apoptosis cell proportion was elevated with increased expression of pro-apoptotic proteins and decreased anti-apoptotic proteins in lncRNA PCAT-1 knock down cells. Forced over-expression of c-myc in PCAT-1 down-regulated CRC cells increased the level of cyclins. The xenograft growth in lncRNA PCAT-1 down-regulated cells was significantly inhibited along with the reduced proliferative cells. SIGNIFICANCE: Our study revealed a tumorigenic effect of lncRNA PCAT-1 in CRC cells, and this effect is partly dependent on the inhibition of c-myc.
[Mh] Termos MeSH primário: Apoptose
Neoplasias Colorretais/genética
Neoplasias Colorretais/patologia
Regulação para Baixo
RNA Longo não Codificante/genética
[Mh] Termos MeSH secundário: Animais
Proteínas Reguladoras de Apoptose/biossíntese
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/genética
Ciclinas/biossíntese
Seres Humanos
Masculino
Camundongos
Proteínas Proto-Oncogênicas c-myc/biossíntese
RNA Longo não Codificante/biossíntese
RNA Interferente Pequeno/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Cyclins); 0 (PCAT-1 lncRNA, human); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Long Noncoding); 0 (RNA, Small Interfering)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE


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[PMID]:28844016
[Au] Autor:Fredholm H; Magnusson K; Lindström LS; Tobin NP; Lindman H; Bergh J; Holmberg L; Pontén F; Frisell J; Fredriksson I
[Ad] Endereço:Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Department of Breast- and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden. Electronic address: hanna.fredholm@ki.se.
[Ti] Título:Breast cancer in young women and prognosis: How important are proliferation markers?
[So] Source:Eur J Cancer;84:278-289, 2017 Oct.
[Is] ISSN:1879-0852
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis. METHODS: Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins. RESULTS: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]). CONCLUSIONS: The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
[Mh] Termos MeSH primário: Neoplasias da Mama/química
Proliferação Celular
Antígeno Ki-67/análise
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Idoso
Neoplasias da Mama/mortalidade
Neoplasias da Mama/patologia
Neoplasias da Mama/terapia
Ciclinas/análise
Intervalo Livre de Doença
Feminino
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Meia-Idade
Valor Preditivo dos Testes
Modelos de Riscos Proporcionais
Receptor ErbB-2/análise
Receptores Estrogênicos/análise
Receptores de Progesterona/análise
Sistema de Registros
Fatores de Risco
Suécia
Fatores de Tempo
Análise Serial de Tecidos
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (Ki-67 Antigen); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE


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[PMID]:28843429
[Au] Autor:Grille Coronel L; Acierno JP; Ermácora MR
[Ad] Endereço:Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Pena 352, B1876BXD Bernal, Pcia. de Buenos Aires, Argentina.
[Ti] Título:Ultracompact states of native proteins.
[So] Source:Biophys Chem;230:36-44, 2017 Nov.
[Is] ISSN:1873-4200
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A statistical analysis of circa 20,000 X-ray structures evidenced the effects of temperature of data collection on protein intramolecular distances and degree of compaction. Identical chains with data collected at cryogenic ultralow temperatures (≤160K) showed a radius of gyration (R ) significantly smaller than at moderate temperatures (≥240K). Furthermore, the analysis revealed the existence of structures with a R significantly smaller than expected for cryogenic temperatures. In these ultracompact cases, the unusually small R could not be specifically attributed to any experimental parameter or crystal features. Ultracompaction involves most atoms and results in their displacement toward the center of the molecule. Ultracompact structures on average have significantly shorter van der Waals and hydrogen bonds than expected for ultralow temperature structures. In addition, the number of van der Waals contacts was larger in ultracompact than in ultralow temperature structures. The structure of these ultracompact states was analyzed in detail and the implication and possible causes of the phenomenon are discussed.
[Mh] Termos MeSH primário: Proteínas/química
[Mh] Termos MeSH secundário: Animais
Bovinos
Quimotripsina/química
Ciclinas/química
Bases de Dados de Proteínas
Fator VII/química
Antígenos HLA-DR/química
Seres Humanos
Ligações de Hidrogênio
Estrutura Terciária de Proteína
Eletricidade Estática
Temperatura Ambiente
Tripsina/química
Microglobulina-2 beta/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclins); 0 (HLA-DR Antigens); 0 (Proteins); 0 (beta 2-Microglobulin); 9001-25-6 (Factor VII); EC 3.4.21.1 (Chymotrypsin); EC 3.4.21.1 (alpha-chymotrypsin); EC 3.4.21.4 (Trypsin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE



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