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1.
Anticancer Res ; 39(9): 4729-4736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519572

RESUMO

BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents. MATERIALS AND METHODS: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients. RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor group showed no survival difference between them. CONCLUSION: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided tumors. This may help explain why left-sided CRC is more responsive to anti-EGFR antibodies.


Assuntos
Anfirregulina/genética , Neoplasias Colorretais/genética , Epirregulina/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Especificidade de Órgãos/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
2.
Anticancer Res ; 39(9): 4743-4748, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519574

RESUMO

BACKGROUND/AIM: Overexpression of human telomerase reverse transcriptase (hTERT) allows disordered proliferation and immortality of malignant cells, which has been of interest for the development of targeted therapies. The present study aimed to characterize hTERT gene expression in a series of cancer cell lines. MATERIALS AND METHODS: Leukemia cell lines K-562, its vincristine-resistant derivative K-562-Lucena1 and daunorubicin-resistant derivative FEPS; gastric adenocarcinoma lines AGP01, ACP02 and ACP03; melanoma SK-Mel-103 cells; and MN01 and MRC5, two non-neoplastic cell lines were analyzed by real-time polymerase chain reaction in order to evaluate hTERT gene expression. RESULTS: In leukemia cells, hTERT gene expression was significantly increased only in K-562 (p<0.05) and K-562-Lucena1 (p<0.001) when compared to the calibrator MRC5. For solid tumor types, only ACP03 presented a significant hTERT gene expression when compared to ACP02 (p<0.05). hTERT gene expression in K-562 and K-562-L ucena was significantly increased (p<0.05 to p<0.001) compared to all other cell lines except ACP03. CONCLUSION: In leukemia cell lines, hTERT gene overexpression was shown to be a potential target for pharmacological assays for drugs aiming to inhibit telomerase activity and control cell proliferation in oncohematological diseases.


Assuntos
Regulação Neoplásica da Expressão Gênica , Telomerase/genética , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Hematológicas/genética , Humanos , Neoplasias/genética , Especificidade de Órgãos/genética
3.
J Cancer Res Clin Oncol ; 145(10): 2413-2422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492983

RESUMO

PURPOSE: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer. METHODS: The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo. CONCLUSIONS: PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.


Assuntos
Biomarcadores Tumorais , Neoplasias/etiologia , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Centrossomo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Especificidade de Órgãos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
5.
Nature ; 571(7766): 510-514, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243368

RESUMO

Although many long noncoding RNAs (lncRNAs) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. In particular, the contribution of lncRNAs to organ development remains largely unexplored. Here we analyse the expression patterns of lncRNAs across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chicken). Our analyses identified approximately 15,000 to 35,000 candidate lncRNAs in each species, most of which show species specificity. We characterized the expression patterns of lncRNAs across developmental stages, and found many with dynamic expression patterns across time that show signatures of enrichment for functionality. During development, there is a transition from broadly expressed and conserved lncRNAs towards an increasing number of lineage- and organ-specific lncRNAs. Our study provides a resource of candidate lncRNAs and their patterns of expression and evolutionary conservation across mammalian organ development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Especificidade de Órgãos/genética , Organogênese/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Especificidade da Espécie , Animais , Atlas como Assunto , Galinhas/genética , Evolução Molecular , Feminino , Humanos , Macaca mulatta/genética , Masculino , Camundongos , Gambás/genética , Proteínas/genética , RNA Longo não Codificante/análise , Coelhos , Ratos
6.
Mol Biol (Mosk) ; 53(3): 485-496, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184614

RESUMO

Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoprotein (HDL). ApoA-I constitutes ~75% of the protein content of HDL. The main sites of ApoA-I synthesis in humans are the liver and the small intestine. The mechanisms that govern tissue-specific apoA-I transcription in tissues and organs other than the liver and the small intestine are poorly understood. It is known that the human apoA-I has two additional promoters, the proximal and the distal one. In this work these two alternative apoA-I promoters are characterized, their transcription start sites are mapped and their competition for apoA-Itranscription is demonstrated; the role of the alternative promoters in apoA-I expression in human cells and tissues other than hepatocytes and enterocytes is discussed.


Assuntos
Apolipoproteína A-I/genética , Regiões Promotoras Genéticas/genética , Sítio de Iniciação de Transcrição , Transcrição Genética/genética , Humanos , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Fígado/citologia , Fígado/metabolismo , Especificidade de Órgãos/genética
7.
J Cancer Res Clin Oncol ; 145(8): 2027-2038, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243545

RESUMO

BACKGROUND: Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important in hepatocellular carcinoma (HCC) development and progression. In this study, we aim to evaluate the expression of lncRNA FAM99B and its biological function in HCC. METHODS: The expression level of FAM99B in HCC was assessed based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), verified using quantitative real-time polymerase chain reaction (qRT-PCR). HCCLM3 was transfected with lentivirus containing full-length FAM99B to obtain stable overexpressing cell line. Cell Counting Kit 8, clone formation, and transwell assays were used to investigate the effects of FAM99B in HCC progression. In addition, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PANTHER pathway analyses were conducted to investigate the underlying molecular mechanisms. RESULTS: FAM99B was found to be downregulated in HCC tissues compared with adjacent normal tissues based on TCGA, GEO, and qRT-PCR data. Our results revealed that downregulated FAM99B was significantly associated with vascular invasion, advanced histologic grade, and T stage. Kaplan-Meier analysis using TCGA data indicated that decreased FAM99B levels were significantly associated with poor overall survival in patients with HCC. Moreover, overexpression of FAM99B significantly inhibited cell proliferation, migration, and invasion in vitro. Pathway analyses showed that the co-expressed genes of FAM99B mainly participated in the pathways "Metabolic pathways" and "Blood coagulation". CONCLUSION: Our results suggest that FAM99B may serve as a tumor suppressor in HCC and may provide a promising therapy target for patients with HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/patologia , Fígado/metabolismo , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Especificidade de Órgãos/genética , RNA Longo não Codificante/genética , Análise de Sobrevida
8.
Int J Mol Sci ; 20(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060255

RESUMO

GSK3 (glycogen synthase kinase 3) is a conserved protein kinase governing numerous regulatory pathways. In Drosophila melanogaster, GSK3 is encoded by shaggy (sgg), which forms 17 annotated transcripts corresponding to 10 protein isoforms. Our goal was to demonstrate how differential sgg transcription affects lifespan, which GSK3 isoforms are important for the nervous system, and which changes in the nervous system accompany accelerated aging. Overexpression of three sgg transcripts affected the lifespan in a stage- and tissue-specific way: sgg-RA and sgg-RO affected the lifespan only when overexpressed in muscles and in embryos, respectively; the essential sgg-RB transcript affected lifespan when overexpressed in all tissues tested. In the nervous system, only sgg-RB overexpression affected lifespan, causing accelerated aging in a neuron-specific way, with the strongest effects in dopaminergic neurons and the weakest effects in GABAergic neurons. Pan-neuronal sgg-RB overexpression violated the properties of the nervous system, including the integrity of neuron bodies; the number, distribution, and structure of mitochondria; cytoskeletal characteristics; and synaptic activity. Such changes observed in young individuals indicated premature aging of their nervous system, which paralleled a decline in survival. Our findings demonstrated the key role of GSK3 in ensuring the link between the pathology of neurons and lifespan.


Assuntos
Proteínas de Drosophila/genética , Drosophila/genética , Regulação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , Estágios do Ciclo de Vida/genética , Longevidade/genética , Animais , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Feminino , Quinase 3 da Glicogênio Sintase/metabolismo , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neurônios/metabolismo , Neurônios/ultraestrutura , Especificidade de Órgãos/genética , Fenótipo
9.
Mol Cell ; 74(4): 640-650, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100245

RESUMO

Cellular RNAs are naturally decorated with a variety of chemical modifications. The structural diversity of the modified nucleosides provides regulatory potential to sort groups of RNAs for organized metabolism and functions, thus affecting gene expression. Recent years have witnessed a burst of interest in and understanding of RNA modification biology, thanks to the emerging transcriptome-wide sequencing methods for mapping modified sites, highly sensitive mass spectrometry for precise modification detection and quantification, and extensive characterization of the modification "effectors," including enzymes ("writers" and "erasers") that alter the modification level and binding proteins ("readers") that recognize the chemical marks. However, challenges remain due to the vast heterogeneity in expression abundance of different RNA species, further complicated by divergent cell-type-specific and tissue-specific expression and localization of the effectors as well as modifications. In this review, we highlight recent progress in understanding the function of N6-methyladenosine (m6A), the most abundant internal mark on eukaryotic mRNA, in light of the specific biological contexts of m6A effectors. We emphasize the importance of context for RNA modification regulation and function.


Assuntos
Adenosina/análogos & derivados , Metilação , RNA Mensageiro/genética , RNA/genética , Adenosina/genética , Células Eucarióticas/metabolismo , Regulação da Expressão Gênica/genética , Especificidade de Órgãos/genética , Processamento Pós-Transcricional do RNA/genética , Transcriptoma
10.
Immunogenetics ; 71(5-6): 407-420, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31037384

RESUMO

Major histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1ß transcripts and homotypic aggregation of RTS11. S25-7 transcript levels remained unchanged in the gill, spleen, and liver and were found to be significantly decreased in head kidney beginning 24 h post-stimulation. Meanwhile, INVX transcript levels remained unchanged in all tissues studied. Both S25-7 and INVX proteins were produced in gill and spleen tissues but their expression was unaffected by immune system stimulation. Surprisingly, neither INVX nor S25-7 protein was detected in the secondary immune organ, the head kidney. Analysis of RTS11 cultures demonstrated that both INVX and S25-7 transcript levels significantly increased at 96 h and 120 h following PMA stimulation before returning to control levels at 168 h. Meanwhile, at the protein level in RTS11, S25-7 remained unchanged while INVX had a significant decrease at 168 h post-stimulation. These results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals.


Assuntos
Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Imunomodulação/genética , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/imunologia , Imunidade Adaptativa , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunização , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Isoformas de Proteínas , Transcriptoma
11.
Int J Mol Sci ; 20(9)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035580

RESUMO

In vitro plant regeneration addresses basic questions of molecular reprogramming in the absence of embryonic positional cues. The process is highly dependent on the genotype and explant characteristics. However, the regulatory mechanisms operating during organ differentiation from in vitro cultures remain largely unknown. Recently, miRNAs have emerged as key regulators during embryogenic callus induction, plant differentiation, auxin responses and totipotency. Here, we explored how development-related miRNA switches the impact on their target regulation depending on physiological and molecular events taking place during maize Tuxpeño VS-535 in vitro plant regeneration. Three callus types with distinctive regeneration potential were characterized by microscopy and histological preparations. The embryogenic calli (EC) showed higher miRNA levels than non-embryogenic tissues (NEC). An inverse correlation for miR160 and miR166 targets was found during EC callus induction, whereas miR156, miR164 and miR394 displayed similar to their targets RNA accumulation levels. Most miRNA accumulation switches took place early at regenerative spots coincident with shoot apical meristem (SAM) establishment, whereas miR156, miR160 and miR166 increased at further differentiation stages. Our data uncover particular miRNA-mediated regulation operating for maize embryogenic tissues, supporting their regulatory role in early SAM establishment and basipetala growth during the in vitro regeneration process.


Assuntos
Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Interferência de RNA , Regeneração/genética , Zea mays/genética , Zea mays/metabolismo , Especificidade de Órgãos/genética , Fenótipo , Desenvolvimento Vegetal/genética , Brotos de Planta/genética , Brotos de Planta/metabolismo
12.
Nat Immunol ; 20(6): 687-700, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061528

RESUMO

Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state and expand during type 2 immunity. Whether shared mechanisms regulate the proliferation of macrophages in homeostasis and disease is unclear. Here we found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages (LPMs), but not that of other tissue-resident macrophages. Bhlhe40 was necessary for the proliferation, but not the polarization, of LPMs in response to the cytokine IL-4. During infection with the helminth Heligmosomoides polygyrus bakeri, Bhlhe40 was required for cell cycling of LPMs. Bhlhe40 repressed the expression of genes encoding the transcription factors c-Maf and Mafb and directly promoted expression of transcripts encoding cell cycle-related proteins to enable the proliferation of LPMs. In LPMs, Bhlhe40 bound to genomic sites co-bound by the macrophage lineage-determining factor PU.1 and to unique sites, including Maf and loci encoding cell-cycle-related proteins. Our findings demonstrate a tissue-specific control mechanism that regulates the proliferation of resident macrophages in homeostasis and type 2 immunity.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Homeodomínio/genética , Homeostase/genética , Homeostase/imunologia , Imunidade/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores , Ciclo Celular/genética , Ciclo Celular/imunologia , Proliferação de Células , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Proteínas de Homeodomínio/metabolismo , Imunofenotipagem , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Transgênicos , Monócitos/imunologia , Monócitos/metabolismo , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Transcriptoma
13.
Nature ; 570(7759): 77-82, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086336

RESUMO

Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.


Assuntos
Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Animais , Diferenciação Celular/genética , Linhagem da Célula/genética , Embrião de Mamíferos/citologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Endoderma/embriologia , Endoderma/metabolismo , Feminino , Fertilização , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento/genética , Masculino , Camundongos , Especificidade de Órgãos/genética , Fenótipo , Análise de Sequência de RNA , Análise de Célula Única
14.
Hum Genet ; 138(6): 661-672, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31069507

RESUMO

Tandem repeats (TRs) are widespread in the genomes of all living organisms. In eukaryotes, they are found in both coding and noncoding regions and have potential roles in the regulation of cellular processes such as transcription, translation and in the modification of protein structure. Recent studies have highlighted TRs as a key regulator of gene expression and a potential contributor to human evolution. Thus, TRs are emerging as an important source of variation that can result in differential gene expression at intra- and inter-species levels. In this study, we performed a genome-wide survey to identify TRs that have emerged in the human lineage. We further examined these loci to explore their potential functional significance for human evolution. We identified 152 human-specific TR (HSTR) loci containing a repeat unit of more than ten bases, with most of them showing a repeat count of two. Gene set enrichment analysis showed that HSTR-associated genes were associated with biological functions in brain development and synapse function. In addition, we compared gene expression of human HSTR loci with orthologues from non-human primates (NHP) in seven different tissues. Strikingly, the expression level of HSTR-associated genes in brain tissues was significantly higher in human than in NHP. These results suggest the possibility that de novo emergence of TRs could have resulted in altered gene expression in humans within a short-time frame and contributed to the rapid evolution of human brain function.


Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica , Especificidade de Órgãos/genética , Sequências de Repetição em Tandem/genética , Animais , Sequência de Bases , Evolução Molecular , Genoma Humano/genética , Humanos , Taxa de Mutação , Primatas/genética , Homologia de Sequência do Ácido Nucleico
15.
BMC Plant Biol ; 19(1): 184, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060496

RESUMO

BACKGROUND: Since their discovery, vacuolar processing enzymes (VPEs) have consistently been investigated as programmed cell death (PCD) initiators and participants in plant development and responses to biotic or abiotic stresses, in part due to similarities with the apoptosis regulator caspase-1. However, recent studies show additional functions of VPE in tomatoes, specifically in sucrose accumulation and fruit ripening. RESULTS: Herein, we evaluated the functions of VPE from sweetpotato, initially in expression pattern analyses of IbVPE1 during development and senescence. Subsequently, we identified physiological functions by overexpressing IbVPE1 in Arabidopsis thaliana, and showed reduced leaf sizes and numbers and early flowering, and elucidated the underlying molecular mechanisms. CONCLUSIONS: The present data demonstrate functions of the VPE gene family in development and senescence and in regulation of flowering times, leaf sizes and numbers, and senescence phenotypes in Arabidopsis thaliana.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Clorofila/metabolismo , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Ipomoea batatas/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Escuridão , Especificidade de Órgãos/genética , Fenótipo , Complexo de Proteína do Fotossistema II/metabolismo , Filogenia , Folhas de Planta/anatomia & histologia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Fatores de Transcrição/metabolismo
16.
BMC Evol Biol ; 19(1): 97, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046675

RESUMO

BACKGROUND: Gene duplication has played an important role in the evolution and domestication of flowering plants. Yet little is known about how plant duplicate genes evolve and are retained over long timescales, particularly those arising from small-scale duplication (SSD) rather than whole-genome duplication (WGD) events. RESULTS: We address this question in the Poaceae (grass) family by analyzing gene expression data from nine tissues of Brachypodium distachyon, Oryza sativa japonica (rice), and Sorghum bicolor (sorghum). Consistent with theoretical predictions, expression profiles of most grass genes are conserved after SSD, suggesting that functional conservation is the primary outcome of SSD in grasses. However, we also uncover support for widespread functional divergence, much of which occurs asymmetrically via the process of neofunctionalization. Moreover, neofunctionalization preferentially targets younger (child) duplicate gene copies, is associated with RNA-mediated duplication, and occurs quickly after duplication. Further analysis reveals that functional divergence of SSD-derived genes is positively correlated with both sequence divergence and tissue specificity in all three grass species, and particularly with anther expression in B. distachyon. CONCLUSIONS: Our results suggest that SSD-derived grass genes often undergo rapid functional divergence that may be driven by natural selection on male-specific phenotypes. These observations are consistent with those in several animal species, suggesting that duplicate genes take similar evolutionary trajectories in plants and animals.


Assuntos
Duplicação Gênica , Variação Genética , Poaceae/genética , Sequência de Bases , Brachypodium/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes Duplicados , Genes de Plantas , Fases de Leitura Aberta/genética , Especificidade de Órgãos/genética , Oryza/genética , Filogenia , Sorghum/genética
17.
Int J Mol Sci ; 20(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934840

RESUMO

Chestnut (Castanea mollissima) is a deciduous tree species with major economic and ecological value that is widely used in the study of floral development in woody plants due its monoecious and out-of-proportion characteristics. Squamosa promoter-binding protein-like (SPL) is a plant-specific transcription factor that plays an important role in floral development. In this study, a total of 18 SPL genes were identified in the chestnut genome, of which 10 SPL genes have complementary regions of CmmiR156. An analysis of the phylogenetic tree of the squamosa promoter-binding protein (SBP) domains of the SPL genes of Arabidopsis thaliana, Populus trichocarpa, and C. mollissima divided these SPL genes into eight groups. The evolutionary relationship between poplar and chestnut in the same group was similar. A structural analysis of the protein-coding regions (CDSs) showed that the domains have the main function of SBP domains and that other domains also play an important role in determining gene function. The expression patterns of CmmiR156 and CmSPLs in different floral organs of chestnut were analyzed by real-time quantitative PCR. Some CmSPLs with similar structural patterns showed similar expression patterns, indicating that the gene structures determine the synergy of the gene functions. The application of gibberellin (GA) and its inhibitor (Paclobutrazol, PP333) to chestnut trees revealed that these exert a significant effect on the number and length of the male and female chestnut flowers. GA treatment significantly increased CmmiR156 expression and thus significantly decreased the expression of its target gene, CmSPL6/CmSPL9/CmSPL16, during floral bud development. This finding indicates that GA might indirectly affect the expression of some of the SPL target genes through miR156. In addition, RNA ligase-mediated rapid amplification of the 5' cDNA ends (RLM-RACE) experiments revealed that CmmiR156 cleaves CmSPL9 and CmSPL16 at the 10th and 12th bases of the complementary region. These results laid an important foundation for further study of the biological function of CmSPLs in the floral development of C. mollissima.


Assuntos
Fagaceae/crescimento & desenvolvimento , Fagaceae/genética , Flores/crescimento & desenvolvimento , Flores/genética , Giberelinas/farmacologia , MicroRNAs/genética , Família Multigênica , Proteínas de Plantas/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência de Bases , Sequência Conservada , Fagaceae/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Inflorescência/efeitos dos fármacos , Inflorescência/genética , MicroRNAs/metabolismo , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Filogenia , Reguladores de Crescimento de Planta/farmacologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Reprodutibilidade dos Testes
18.
Sci Data ; 6(1): 36, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015567

RESUMO

Comprehensive analysis of molecular pathology requires a collection of reference samples representing normal tissues from healthy donors. For the available limited collections of normal tissues from postmortal donors, there is a problem of data incompatibility, as different datasets generated using different experimental platforms often cannot be merged in a single panel. Here, we constructed and deposited the gene expression database of normal human tissues based on uniformly screened original sequencing data. In total, 142 solid tissue samples representing 20 organs were taken from post-mortal human healthy donors of different age killed in road accidents no later than 36 hours after death. Blood samples were taken from 17 healthy volunteers. We then compared them with the 758 transcriptomic profiles taken from the other databases. We found that overall 463 biosamples showed tissue-specific rather than platform- or database-specific clustering and could be aggregated in a single database termed Oncobox Atlas of Normal Tissue Expression (ANTE). Our data will be useful to all those working with the analysis of human gene expression.


Assuntos
Bases de Dados Genéticas , Especificidade de Órgãos/genética , Análise de Sequência de RNA , Transcriptoma , Perfilação da Expressão Gênica , Humanos
19.
BMC Plant Biol ; 19(1): 160, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023213

RESUMO

BACKGROUND: Sugarcane accumulates very high levels of sucrose in the culm. Elucidation of the molecular mechanisms that allows such high sucrose synthesis and accumulation (up to 650 mM) is made difficult by the complexity of the highly polyploid genome. Here we report the use of RNA Seq data to characterize the sucrose synthase (SuSy) genes expressed in the transcriptome of the mature sugarcane plant. RESULTS: Four SuSy gene families were identified in the sugarcane Iso-Seq long read transcriptome (SUGIT) through gene annotation of transcripts that mapped to reference SuSy genes from sorghum and maize. In total, 38, 19, 14, and 2 transcripts were identified for the four corresponding SuSy genes 1, 2, 4 and 7, respectively. Comparative studies using available SuSy genes from sorghum (1, 2, 4, 6, 7) and maize (1-7) revealed that the sugarcane SuSy genes were interrupted by multiple introns and that they share a highly conserved gene structure. Spatial expression of the four SuSy genes in sugarcane genotypes and in the progenitor species, Saccharum spontaneum and Saccharum officinarum, was studied in the leaf and root tissues and also in three regions of the culm tissue; top, middle and bottom internodes. Expression profiles indicated that all SuSy transcripts were differentially expressed between the top and bottom tissues, with high expression in the top tissues, lower expression in the bottom and moderate expression in the middle, indicating a gradient of SuSy activity in the sugarcane culm. Further, the root tissue had similar expression levels to that of the top internodes while leaf tissues showed lower expression. In the progenitors, SuSy7 was found to be highly expressed in S. officinarum while the other three SuSy genes had moderate expression in both the progenitors. CONCLUSIONS: The high expression of the SuSy genes in sink tissues, the top internodes and the roots suggests functional roles in sucrose utilization to support growth. The SuSy7 gene has not been previously reported in sugarcane. As sugarcane is unique in storing such high amounts of sucrose, it is possible that there are more SuSy genes/isoforms with specific expression patterns to be discovered in this complex system.


Assuntos
Genes de Plantas , Variação Genética , Glucosiltransferases/genética , Especificidade de Órgãos/genética , Saccharum/genética , Transcriptoma/genética , Éxons/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Íntrons/genética , Fases de Leitura Aberta/genética , Oryza/genética , Filogenia , Sorghum/genética , Zea mays/genética
20.
Int J Mol Sci ; 20(6)2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30934541

RESUMO

Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy. Comparing the biological and transcriptome gene characteristics of MSCs from different sources provides an important basis for the screening of clinically used cells. The main purpose of this experiment was to establish methods for the isolation and culture of MSCs from five different canine sources, including adipose tissue, bone marrow, umbilical cord, amniotic membrane, and placenta, and compare biological and transcriptome characteristics of MSCs, in order to provide a basis for the clinical application of canine MSCs. MSCs were isolated from Chinese pastoral dogs, and the following experiments were performed: (1) the third, sixth, and ninth generations of cells were counted, respectively, and a growth curve was plotted to calculate the MSC population doubling time; (2) the expression of CD34 and CD44 surface markers was studied by immunofluorescence; (3) the third generation of cells were used for osteogenetic and adipogenic differentiation experiments; and (4) MSC transcriptome profiles were performed using RNA sequencing. All of the five types of MSCs showed fibroblast-like adherent growth. The cell surface expressed CD44 instead of CD34; the third-generation MSCs had the highest proliferative activity. The average population doubling time of adipose mesenchymal stem cells (AD-MSCs), placenta mesenchymal stem cells (P-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), and amniotic mesenchymal stem cells (AM-MSCs) were 15.8 h, 21.2 h, 26.2 h, 35 h, and 41.9 h, respectively. All five types of MSCs could be induced to differentiate into adipocytes and osteoblasts in vitro, with lipid droplets appearing after 8 days and bone formation occurring 5 days after AD-MSC induction. However, the multilineage differentiation for the remaining of MSCs was longer compared to that of the AD-MSCs. The MSC transcriptome profiles showed that AD-MSC and BM-MSCs had the highest homology, while P-MSCs were significantly different compared to the other four types of MSCs. All the isolated MSCs had the main biological characteristics of MSCs. AD-MSCs had the shortest time for proliferation, adipogenesis, and osteogenic differentiation.


Assuntos
Cães/genética , Células-Tronco Mesenquimais/metabolismo , Especificidade de Órgãos/genética , Transcriptoma/genética , Animais , Biomarcadores/metabolismo , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Análise por Conglomerados , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Reprodutibilidade dos Testes
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