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1.
Cell Death Dis ; 11(5): 400, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457294

RESUMO

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is the core component of DNA-PK complex in the non-homologous end-joining (NHEJ) repair of DNA double-strand breaks, and its activity is strictly controlled by DNA-PKcs phosphorylation. The ubiquitin-like protein, NEDD8 is involved in regulation of DNA damage response, but it remains mysterious whether and how NEDD8-related neddylation affects DNA-PKcs and the NHEJ process. Here, we show that DNA-PKcs is poly-neddylated at its kinase domain. The neddylation E2-conjugating enzyme UBE2M and E3 ligase HUWE1 (HECT, UBA, and WWE domain containing E3 ubiquitin protein ligase 1) are responsible for the DNA-PKcs neddylation. Moreover, inhibition of HUWE1-dependent DNA-PKcs neddylation impairs DNA-PKcs autophosphorylation at Ser2056. Finally, depletion of HUWE1-dependent DNA-PKcs neddylation reduces the efficiency of NHEJ. These studies provide insights how neddylation modulates the activity of NHEJ core complex.

2.
Cell Death Differ ; 27(4): 1383-1397, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31562368

RESUMO

End resection of DNA double-strand breaks (DSBs) to form 3' single-strand DNA (ssDNA) is critical to initiate the homologous recombination (HR) pathway of DSB repair. HR pathway is strictly limited in the G1-phase cells because of lack of homologous DNA as the templates. Exonuclease 1 (EXO1) is the key molecule responsible for 3' ssDNA formation of DSB end resection. We revealed that EXO1 is inactivated in G1-phase cells via ubiquitination-mediated degradation, resulting from an elevated expression level of RING-box protein 1 (RBX1) in G1 phase. The increased RBX1 significantly prompted the neddylation of Cullin1 and contributed to the G1 phase-specific degradation of EXO1. Knockdown of RBX1 remarkedly attenuated the degradation of EXO1 and increased the end resection and HR activity in γ-irradiated G1-phase cells, as demonstrated by the increased formation of RPA32, BrdU, and RAD51 foci. And EXO1 depletion mitigated DNA repair defects due to RBX1 reduction. Moreover, increased autophosphorylation of DNA-PKcs at S2056 was found to be responsible for the higher expression level of the RBX1 in the G1 phase. Inactivation of DNA-PKcs decreased RBX1 expression, and simultaneously increased EXO1 expression and DSB end resection in G1-phase cells. This study demonstrates a new mechanism for restraining the HR pathway of DNA DSB repair in G1 phase via RBX1-prompted inactivation of EXO1.

3.
J Cancer ; 10(25): 6466-6474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772679

RESUMO

The establishment of human malignant tumor cell lines can provide abundant experimental materials for understanding the biological characteristics of tumors, studying the carcinogenesis, molecular genetics and the mechanism of metastasis and evolution. In this study, a novel cell line designated ZJB-ENC1 has been established from poorly differentiated endometrioid adenocarcinoma. Cytological results showed monolayer-cultured cells were polygonal in shape and a piling-up tendency without contact inhabitation. Immunohistochemistry analysis showed that the cells were negative for ER, PR, c-erbB2, E-CAD, CD117, and OCT3/4, but strongly positive for PTEN and P16. Meanwhile, the tumorigenicity of ZJB-ENC1 was confirmed by subcutaneous transplantation of the cells into a xenograft mouse model. In addition, the results of the whole exome sequencing revealed a unique genomic characteristic of ZJB-ENC1 cells, all common and novel SNPs and InDels were identified. In conclusion, this new stable cell line may promote basic and clinical research on endometrial cancer (EC).

4.
Dose Response ; 17(1): 1559325819833474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30833875

RESUMO

Background: Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level. Materials and Methods: Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles. Results: Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), HBG2(hemoglobin subunit gamma 2), TNFAIP3 (TNF α-induced protein 3), PER1 (period circadian clock 1), CCDC136 (coiled-coil domain containing 136), C9orf84 (chromosome 9 open reading frame 84), IL1B (interleukin 1ß), FOSB (FosB protooncogene), NR4A2 (nuclear receptor subfamily 4), PARP15 (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (ALAS2, FOSB, and HBG2) are suggested as potential predictors for the early diagnosis of HT after RT. Conclusions: ALAS2, FOSB, and HBG2 may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.

5.
Int J Radiat Biol ; 95(2): 144-155, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30395764

RESUMO

PURPOSE: To identify the mRNA and long noncoding RNA (lncRNA) expression profiles and explore the lncRNA-mRNA co-expression networks associated with the carcinogenesis induced by α-particles. MATERIALS AND METHODS: Immortalized human bronchial epithelial cell line, BEP2D, and its two malignant transformed cell lines, BERP35T-1 and BERP35T-4, were investigated. The lncRNA and mRNA expression profiles of BEP2D, BERP35T-1 and BERP35T-4 were generated. lncRNAs and mRNAs co-expression analysis was performed. RESULTS: The microarray identified 668 lncRNAs in BERP35T-1 cells and 555 in BERP35T-4 cells that were differentially expressed compared to BEP2D cells. The GO terms and KEGG pathway annotation data indicated that mitotic cell cycle, DNA repair, apoptotic processes, and RNA splicing functional pathways were significantly associated with the α-particle induced cell carcinogenesis. Co-expression network analysis revealed 8902 interactions between 495 differentially expressed mRNAs and 430 corresponding lncRNAs in BERP35T-1 cells compared with BEP2D cells. The genes, situated at the important nodes of the co-expression network, include B3GNT5, RAD23, YWHAZ (14-3-3ζ), FBXW11, TGFBR2, LRP6, PSMD11, MYL12A, etc. Conclusions: This pilot study is the first to explore epigenetic mechanisms of α-particle induced carcinogenesis of human bronchial epithelial cells. It provides basic information for further investigation into the detail mechanisms underlying radiation-induced lung cancer.


Assuntos
Partículas alfa/efeitos adversos , Carcinogênese , RNA Longo não Codificante/análise , RNA Mensageiro/análise , Células Cultivadas , Análise por Conglomerados , Células Epiteliais/patologia , Humanos , Projetos Piloto , Transcriptoma
6.
Br J Cancer ; 119(4): 492-502, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30038324

RESUMO

BACKGROUND: An increasing number of studies have recently reported that microRNAs packaged in exosomes contribute to multiple biological processes such as cancer progression; however, little is known about their role in the development of radiation-induced bystander effects. METHODS: The exosomes were isolated from the culture medium of BEP2D cells with or without γ-ray irradiation by ultracentrifugation. To monitor DNA damage and repair efficiency, the DNA double-strand break biomarker 53BP1 foci, comet, micronuclei, expression of DNA repair genes and NHEJ repair activity were detected. The miR-1246 targeting sequence of the DNA ligase 4 (LIG4) mRNA 3'UTR was assessed by luciferase reporter vectors. RESULTS: miR-1246 was increased in exosomes secreted from 2 Gy-irradiated BEP2D cells and inhibited the proliferation of nonirradiated cells. The miR-1246 mimic, exosomes from irradiated cells, and radiation-conditioned cell culture medium increased the yields of 53BP1 foci, comet tail and micronuclei in nonirradiated cells, and decreased NHEJ efficiency. miR-1246 downregulated LIG4 expression by directly targeting its 3'UTR. CONCLUSIONS: Our findings demonstrate that miR-1246 packaged in exosomes could act as a transfer messenger and contribute to DNA damage by directly repressing the LIG4 gene. Exosomal miR-1246 may be a critical predictor of and player in radiation-induced bystander DNA damage.


Assuntos
DNA Ligase Dependente de ATP/genética , Regulação para Baixo , Exossomos/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Efeito Espectador , Linhagem Celular , Proliferação de Células/efeitos da radiação , Meios de Cultivo Condicionados/química , Dano ao DNA , Exossomos/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Células HEK293 , Humanos , Análise de Sequência de DNA
7.
Oncol Lett ; 16(1): 431-438, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29928431

RESUMO

Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53+/+) and depleted HCT116 (HCT116 p53-/-) cells were used throughout this study. Cells carrying the CSC biomarkers CD133 and CD44 were examined by flow cytometry. A dual-luciferase reporter assay was employed to further confirm the transcriptional regulation of the CD133 promoter by p53. The results demonstrated that there was a significant difference in the % of CD133-positive cells between the HCT116 p53+/+ cell line (84.84±0.05%) and the HCT116 p53-/- cell line (4.13±0.02%). The mRNA expression levels of CD133 in HCT116 p53+/+ cells were also significantly higher compared with HCT116 p53-/- cells. Knockdown of p53 by specific small interfering RNA greatly reduced the expression of CD133 in HCT116 p53+/+ cells. Transcription factor binding site analysis indicated that there are several p53 binding elements in the CD133 promoter region. A dual-luciferase reporter assay further demonstrated the transcriptional activation of CD133 promoter by p53. In conclusion, these results suggest that p53 positively regulates the expression of CSC marker CD133 in the HCT116 human colon colorectal cancer cell line. p53 may be involved in the initiation and maintenance of colorectal cancer stem cells through regulating the expression of CD133.

8.
Oncol Lett ; 14(2): 2305-2309, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781668

RESUMO

The purpose of this study was to investigate the expression of miR-375 and miR-221 in liver cancer, and examine the correlations with pathological parameters and prognosis. We collected tumors and tumor-adjacent normal tissue from 70 patients with liver cancer admitted to the Department of General Surgery of Zhejiang Hospital. The expression of miR-375 by RT-qPCR was significantly lower in liver cancer tissues than that in the tumor-adjacent normal tissues, and the low expression was correlated with the lymphatic metastasis and TNM stage. By contrast, the expression of miR-221 was significantly higher in liver cancer than that in the tumor-adjacent tissues, and the high expression was correlated with the lymphatic metastasis and TNM stage. The overall 5-year survival rate of patients was 12.9% (9/70). Single-factor survival analysis revealed that miR-375 and miR-221 were the factors affecting the overall survival rate of liver cancer (P<0.05) and multivariate survival analysis by Cox proportional hazards model showed that miR-375 and miR-221 were the independent factors affecting the survival time of patients with liver cancer. Low expression of miR-375 and high expression of miR-221 are closely correlated with the occurrence and development of liver cancer, especially lymphatic metastasis and TNM stage. Thus, miR-375 and miR-221 can serve as reference biomarkers for guiding the treatment of liver cancer and for estimating prognosis.

9.
Oncol Lett ; 14(2): 1455-1459, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789364

RESUMO

The effects of naringin on the expression of miR-19b and cell apoptosis were investigated in the human hepatocellular carcinoma cell line HepG2. HepG2 cells were treated with varied concentrations of naringin. The effects of naringin on the proliferation of HepG2 cells were observed by an MTT assay, morphological changes of cells were observed by an inverted microscope, cell apoptosis was detected by DAPI staining, miR-19b mRNA levels were determined with RT-PCR, and the expression of Bax and Bcl-2 proteins was examined by western blot assay. MTT results showed that naringin significantly inhibited the proliferation of HepG2 cells. Apoptotic HepG2 cells showed obvious changes in morphology under inverted microscope. DAPI staining suggested that naringin could induce cell shrinkage and nuclear chromatin condensation. RT-PCR results showed that naringin could upregulate the expression of miR-19b mRNA. Finally, western blot suggested that naringin upregulated the expression of Bax protein, but downregulated the expression of Bcl-2 protein. In conclusion, naringin can upregulate the expression of miR-19b mRNA and induce HepG2 cell apoptosis. In addition, it can also upregulate the expression of Bax protein and downregulate the expression of Bcl-2 protein during the process of apoptosis.

10.
PLoS One ; 11(10): e0163896, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27711237

RESUMO

Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion 12C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)-Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/µm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/µm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/µm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general.


Assuntos
Carbono/farmacologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteômica , RNA/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta à Radiação , Radioterapia com Íons Pesados , Camundongos
11.
Pharmacol Res ; 113(Pt A): 475-483, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27664700

RESUMO

Exposure to ionizing radiation causes damage to living tissues; however, only a small number of agents have been approved for use in radiation injuries. Radioprotector is the primary countermeasure to radiation injury and none radioprotector has indeed reached the drug development stage. Repurposing the long list of approved, non-radioprotective drugs is an attractive strategy to find new radioprotective agents. Here, we applied a computational approach to discover new radioprotectors in silico by comparing publicly available gene expression data of ionizing radiation-treated samples from the Gene Expression Omnibus (GEO) database with gene expression signatures of more than 1309 small-molecule compounds from the Connectivity Map (cmap) dataset. Among the best compounds predicted to be therapeutic for ionizing radiation damage by this approach were some previously reported radioprotectors and baclofen (P<0.01), a chemical that was not previously used as radioprotector. Validation using a cell-based model and a rodent in vivo model demonstrated that treatment with baclofen reduced radiation-induced cytotoxicity in vitro (P<0.01), attenuated bone marrow damage and increased survival in vivo (P<0.05). These findings suggest that baclofen might serve as a radioprotector. The drug repurposing strategy by connecting the GEO data and cmap can be used to identify known drugs as potential radioprotective agents.


Assuntos
Baclofeno/farmacologia , Protetores contra Radiação/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Reposicionamento de Medicamentos/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma/efeitos dos fármacos
12.
Sci Rep ; 6: 30165, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27417393

RESUMO

Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy.


Assuntos
Autofagia/fisiologia , Brônquios/metabolismo , Efeito Espectador/fisiologia , Células Epiteliais/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Linhagem Celular , Humanos , Radiação Ionizante , Transdução de Sinais/fisiologia
13.
Sci Rep ; 5: 15820, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26508266

RESUMO

Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust "HTR communities" (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.


Assuntos
Transcrição Genética/genética , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Genoma Humano/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reprodutibilidade dos Testes
14.
Mol Biosyst ; 11(9): 2511-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26166390

RESUMO

Genome-wide RNA interference screens have greatly facilitated the identification of essential host factors (EHFs) for viral infections, whose knockdown effects significantly influence virus replication but not host cell viability. However, little has been done to link EHFs with another important host factor type, i.e., virus targeting proteins (VTPs) that viruses directly interact with for intracellular survival, hampering the integrative understanding of virus-host interactions. Using EHFs and VTPs for human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV) infections, we found in general that despite limited overlap, EHFs and VTPs are both among the most differentially dysregulated genes in host transcriptional response to HIV and IAV infections, and notably they show consistency in regulation orientation. In the human protein-protein interaction network, both EHFs and VTPs hold topologically important positions at the global center, and importantly their direct interactions are statistically significant. We also identified BRCA1 and TP53 (or SMAD3 and PIK3R1) being the most extensive VTP-interacting EHFs (or EHF-interacting VTPs) for HIV-1 and IAV, which hold great potential in deciphering specific infection features and discovery of host directed antivirals. Further, most EHFs are the upstream regulators of VTPs when mapped in the same signaling pathways, some of which present intensive cross links. Collectively, these results provide insights into functional associations of the identified host gene factors for viral infections and highlight the regulatory significance of EHFs, and the necessity of their selective exploitation in confrontation to viral infections.


Assuntos
Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Interferência de RNA , Proteínas Virais/metabolismo , Viroses/genética , Viroses/metabolismo , Análise por Conglomerados , Perfilação da Expressão Gênica , HIV-1/fisiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Vírus da Influenza A/fisiologia , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transdução de Sinais , Transcrição Genética
15.
Nucleic Acids Res ; 43(Database issue): D946-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25414353

RESUMO

High-throughput screening and computational technology has greatly changed the face of microbiology in better understanding pathogen-host interactions. Genome-wide RNA interference (RNAi) screens have given rise to a new class of host genes designated as Essential Host Factors (EHFs), whose knockdown effects significantly influence pathogenic infections. Therefore, we present the first release of a manually-curated bioinformatics database and analysis resource EHFPI (Essential Host Factors for Pathogenic Infection, http://biotech.bmi.ac.cn/ehfpi). EHFPI captures detailed article, screen, pathogen and phenotype annotation information for a total of 4634 EHF genes of 25 clinically important pathogenic species. Notably, EHFPI also provides six powerful and data-integrative analysis tools, i.e. EHF Overlap Analysis, EHF-pathogen Network Analysis, Gene Enrichment Analysis, Pathogen Interacting Proteins (PIPs) Analysis, Drug Target Analysis and GWAS Candidate Gene Analysis, which advance the comprehensive understanding of the biological roles of EHF genes, as in diverse perspectives of protein-protein interaction network, drug targets and diseases/traits. The EHFPI web interface provides appropriate tools that allow efficient query of EHF data and visualization of custom-made analysis results. EHFPI data and tools shall keep available without charge and serve the microbiology, biomedicine and pharmaceutics research communities, to finally facilitate the development of diagnostics, prophylactics and therapeutics for human pathogens.


Assuntos
Bases de Dados Genéticas , Interações Hospedeiro-Patógeno/genética , Reposicionamento de Medicamentos , Genes , Humanos , Infecções/genética , Vírus da Influenza A/genética , Fenótipo , Mapeamento de Interação de Proteínas , Interferência de RNA , Software
16.
OMICS ; 17(2): 116-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23374109

RESUMO

Comparisons of gene expression signatures provide a way to explore functional connections among biological events in global aspects of cell response. GeneExpressionSignature is an R package developed for the large-scale analysis of gene expression signatures. The package implements two rank-merging algorithms and two similarity-scoring algorithms. The functions of GeneExpressionSignature provide a flexible solution for gene expression signature-based studies and hold great potential in biomedical research applications, such as drug repurposing. GeneExpressionSignature is released under GPL v2 within the Bioconductor project and is freely available at http://www.bioconductor.org/packages/release/bioc/html/GeneExpressionSignature.html .


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica , Software , Transcriptoma , Algoritmos , Linhagem Celular , Análise por Conglomerados , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Internet
17.
Conf Proc IEEE Eng Med Biol Soc ; 2011: 6857-60, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22255914

RESUMO

Functional comparison and alignment of Protein Interaction Networks (PINs) will enable a better understanding of cellular organization and processes. Gene Ontology (GO) provides a structured standard vocabulary of functional terms of gene products, and has been used to measure the functional similarity between proteins. In this study, we propose an algorithm to measure the functional similarity between PINs based on GO. The algorithm simultaneously takes the PIN's network topology and semantic similarity of the component proteins into account. We employ the algorithm to measure the similarity between pathways present in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and cluster the pathways according to similarity. The results show great consistency with the function of these pathways.


Assuntos
Perfilação da Expressão Gênica , Algoritmos , Análise por Conglomerados , Biologia Computacional/métodos , Bases de Dados de Proteínas , Regulação da Expressão Gênica , Genoma , Humanos , Internet , Modelos Genéticos , Modelos Estatísticos , Processamento de Linguagem Natural , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas , Transdução de Sinais
18.
Int J Oncol ; 37(6): 1515-20, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21042720

RESUMO

A serum-specific protein 'fingerprint' model was established which is capable of evaluating the effect of chemotherapy (gemcitabine) of pancreatic adenocarcinoma. We used SELDI-TOF-MS coupled with CM10 chips and bioinformatics tools to analyze a total of 45 mouse serum samples from three groups: the healthy control group, the pancreatic cancer model group (orthotopic transplantation model of human pancreatic adenocarcinoma) and the gemcitabine-treated group to establish diagnostic models. As a result, the test set yielded a specificity of 95.0% and a sensitivity of 95.0% for pattern 1, which distinguished pancreatic adenocarcinoma from healthy individuals and a specificity of 95.0% and a sensitivity of 75.0% for pattern 3, which distinguished healthy controls, PC model group and gemcitabine-treated group, as evaluated by leave-one-out cross-validation. We concluded from this study that the SELDI-TOF-MS technique combined with bioinformatics approaches can facilitate evaluating the effect of chemotherapy (gemcitabine) for pancreatic adenocarcinoma and could be used as a potential prognostic monitoring method.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/prevenção & controle , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/prevenção & controle , Análise Serial de Proteínas , Adenocarcinoma/metabolismo , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Quimioprevenção/métodos , Desoxicitidina/uso terapêutico , Técnicas de Diagnóstico Endócrino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Resultado do Tratamento , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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