Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
World J Gastroenterol ; 25(35): 5300-5309, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558874

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A's role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM: To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS: The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS: CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION: Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.

3.
Gene ; 707: 44-52, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30898716

RESUMO

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aims to investigate the role and mechanism of LINC00520 in the NPC carcinogenesis. Results indicated that LINC00520 was significantly increasing in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00520 indicated the poor prognosis of NPC patients. Silence of LINC00520 was able to repress NPC cell growth in vitro while overexpression of LINC00520 inversed this process. Moreover, in vivo tumor xenografts were establishing using CNE-1/SUNE-1 cells to investigate the function of LINC00520 in NPC tumorigenesis. Rescue assay was conducting to further confirm that LINC00520 contributed to NPC progression by regulating miR-26b-3p/ubiquitin-specific protease 39 (USP39) signal pathway. Taken together, our study discovered the oncogenic role of LINC00520 in clinical specimens and cellular experiments, showing the potential LINC00520/miR-26b-3p/USP39 pathway. This results and findings provide a novel insight for NPC tumorigenesis.


Assuntos
MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Proteases Específicas de Ubiquitina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Transplante de Neoplasias , Prognóstico , Proteases Específicas de Ubiquitina/metabolismo , Regulação para Cima
4.
Genome Biol Evol ; 11(1): 72-85, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30517636

RESUMO

Yak is one of the largest native mammalian species at the Himalayas, the highest plateau area in the world with an average elevation of >4,000 m above the sea level. Yak is well adapted to high altitude environment with a set of physiological features for a more efficient blood flow for oxygen delivery under hypobaric hypoxia. Yet, the genetic mechanism underlying its adaptation remains elusive. We conducted a cross-tissue, cross-altitude, and cross-species study to characterize the transcriptomic landscape of domestic yaks. The generated multi-tissue transcriptomic data greatly improved the current yak genome annotation by identifying tens of thousands novel transcripts. We found that among the eight tested tissues (lung, heart, kidney, liver, spleen, muscle, testis, and brain), lung and heart are two key organs showing adaptive transcriptional changes and >90% of the cross-altitude differentially expressed genes in lung display a nonlinear regulation. Pathways related to cell survival and proliferation are enriched, including PI3K-Akt, HIF-1, focal adhesion, and ECM-receptor interaction. These findings, in combination with the comprehensive transcriptome data set, are valuable to understanding the genetic mechanism of hypoxic adaptation in yak.


Assuntos
Adaptação Biológica , Altitude , Bovinos/metabolismo , Transcriptoma , Animais , Bovinos/genética , Expressão Gênica , Hipóxia/metabolismo , Pulmão/metabolismo , Masculino , Anotação de Sequência Molecular , Miocárdio/metabolismo , Transdução de Sinais
6.
Onco Targets Ther ; 11: 7821-7825, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464529

RESUMO

Small intestinal metastases from primary lung cancer are rare. Such patients have a poor prognosis. Early diagnosis of small intestinal metastases is difficult because of the low incidence of clinically apparent symptoms. The standard treatment for small intestinal metastases has not been established. A 69-year-old Chinese man presented for evaluation of a tumor in the right lower lung and mediastinal lymph node enlargement on clinical examination. The clinical stage was cT2N2M0 (stage IIIA). Histologic examination of the tumor revealed lung adenocarcinoma. He could not tolerate surgery; hence, he received two chemotherapy regimens. However, the disease progressed. He had bloating after chemotherapy and decreased flatus. An abdominal CT scan showed an intestinal effusion with local intestinal obstruction. Medical treatment was ineffective; hence, he underwent a diagnostic laparoscopy. The pathologic evaluation suggested an intestinal metastatic adenocarcinoma from the primary lung cancer. Based on an real-time PCR assay, the tumor had a ROS1 fusion and responded well to crizotinib. The progression-free survival was 7 months. Physicians must be aware of the possibility of intestinal metastases from primary lung cancer. With an accurate diagnosis and thorough evaluation, patients may benefit from targeted therapy.

8.
Blood ; 131(11): 1183-1194, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29229594

RESUMO

In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n = 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiocinas/sangue , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Recidiva , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia
9.
Oncol Lett ; 13(2): 949-954, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28356983

RESUMO

The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo. The cytotoxicity of TCN was dose dependent. Upon exposure to TCN, ESCC cells in hypoxia treated with 4-Gy radiotherapy exhibited an evidently higher apoptotic rate than cells subjected to other treatments. TCN could significantly inhibit the protein expression of p-AKT, HIF-1α and VEGF in vitro and in vivo. The present results suggested that TCN can effectively inhibit AKT, p-AKT, HIF-1α and VEGF, thus conferring radiosensitivity to ESCC in vitro and vivo. TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.

10.
Mol Biol Evol ; 34(4): 818-830, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28096303

RESUMO

Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2α (HIF-2α) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans. Furthermore, we found that the Tibetan version of EPAS1 is not only associated with the relatively low hemoglobin level as a polycythemia protectant, but also is associated with a low pulmonary vasoconstriction response in Tibetans. We propose that the down-regulation of EPAS1 contributes to the molecular basis of Tibetans' adaption to high-altitude hypoxia.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia/genética , Aclimatação/genética , Adaptação Biológica/genética , Adaptação Fisiológica/genética , Adulto , Altitude , Doença da Altitude/genética , Doença da Altitude/metabolismo , Animais , Regulação para Baixo , Grupos Étnicos/genética , Feminino , Variação Genética/genética , Hemoglobinas , Humanos , Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Desequilíbrio de Ligação/genética , Masculino , Camundongos , Camundongos Knockout , Polimorfismo de Nucleotídeo Único , Seleção Genética , Tibet
11.
Sci Rep ; 6: 32598, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27600022

RESUMO

Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3-6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation.


Assuntos
Segregação de Cromossomos/genética , Evolução Molecular , Macaca fascicularis/genética , Macaca mulatta/genética , Retroelementos/genética , Animais , Sequência de Bases , Biologia Computacional , Simulação por Computador , Regulação da Expressão Gênica , Ontologia Genética , Genética Populacional , Genoma , Funções Verossimilhança , Anotação de Sequência Molecular , Filogenia , Especificidade da Espécie
12.
Chem Commun (Camb) ; 51(50): 10182-5, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-26012496

RESUMO

Three amino-functionalized fluorene oligomers with different solubility were developed as cathode interfacial materials for inverted polymer solar cells (I-PSCs). By side chain design, we solved the interface layer erosion problem for I-PSCs, and the devices exhibit a power conversion efficiency as high as 8.94%.

13.
Int J Clin Exp Med ; 8(11): 20596-602, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26884978

RESUMO

IGF-I CA repeat polymorphisms, especially the allele containing CA19 repeats, have been reported to be associated with the risk for various types of cancers. However, the results still remain controversial and ambiguous. This meta-analysis was performed to evaluate the association between IGF-I CA19 repeat polymorphisms and the risk of cancer. Total 18 studies with IGF-I CA19 repeat genotyping on 9,873 patients and 15,607 controls were analyzed. We used random-effects model with a pooled OR of 0.69 (95% CI = 0.60-0.79) for the recessive genetic model, 0.97 (95% CI = 0.86-1.10) for the dominant genetic model, 0.99 (95% CI = 0.86-1.14) for the homozygote comparison and 1.06 (95% CI = 0.91-1.23) for the heterozygote comparison. In the subgroup analysis of recessive model, OR (95% CI) was 0.65 (0.52-0.80) in breast cancer, 0.68 (0.53-0.86) in prostate cancer, and 0.71 (0.52-0.96) in Caucasian. In conclusion, IGF-1 CA19 repeat polymorphisms are unlikely to be a major determinant of susceptibility to cancer. However, the subgroup analysis of recessive model indicates that IGF-I CA19 repeat polymorphisms may reduce the risk of certain types of cancer or in a specific population.

14.
Tumour Biol ; 36(3): 2135-42, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25492480

RESUMO

The radioresistance of esophageal squamous cell carcinoma (ESCC) remains an obstacle for the effective radiotherapy of ESCC. This study aimed to investigate the radiosensitization of ESCC by signal transducer and activator of transcription 3 (STAT3) inhibitor stattic. ECA109, TE13, and KYSE150 cell lines were exposed to hypoxia and treated with stattic or radiation, alone or in combination. Cell proliferation, colony formation, apoptosis, and double-stranded DNA breaks (DSBs) were examined. In addition, ECA109 cells were xenografted into nude mice and treated with radiation and/or stattic. The levels of STAT3, p-STAT3, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in ESCC cells and xenografts were detected by Western blot and immunohistochemical analysis. Our results showed that stattic efficiently radiosensitized ESCC cells and xenografts, especially under hypoxia. Moreover, stattic inhibited STAT3 activation and downregulated HIF-1α and VEGF expression. In conclusion, stattic confers radiosensitivity in ESCC cells in vitro and in vivo and is a potential adjuvant for the radiotherapy of ESCC in the clinical setting.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Óxidos S-Cíclicos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Regulação para Baixo/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/ultraestrutura , Carcinoma de Células Escamosas do Esôfago , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição STAT3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Tumour Biol ; 35(10): 9793-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24981247

RESUMO

Radiotherapy is the main therapy for inoperable and locally advanced esophageal squamous cell carcinoma (ESCC). However, radioresistance in ESCC remains a challenge. The aim of this study is to investigate the radiosensitizing effects of STAT3 inhibitor NSC74859 on ESCC and explore the underlying mechanisms. ECA109 and TE13 cells were exposed to hypoxia, and treated with NSC74859 or radiation, alone or in combination. Cell proliferation, survival, apoptosis, and double-stranded DNA breaks (DSBs) were examined. Nude mice model of ECA109 xenograft was treated with radiation and/or NSC74859. The levels of STAT3, p-STAT3, HIF-1α, and VEGF were detected by Western blot analysis. NSC74859 efficiently radiosensitized ESCC cells and xenografts in nude mice, and inhibited hypoxia-/radiation-induced activation of STAT3 and upregulation of HIF-1α and VEGF expression. NSC74859 confers radiosensitivity in ESCC via the inhibition of STAT3 activation and the downregulation of HIF-1α and VEGF expression. NSC74859 may become a promising radiosensitizer for ESCC radiotherapy.


Assuntos
Benzenossulfonatos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Radiossensibilizantes/farmacologia , Ácidos Aminossalicílicos/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Regulação para Baixo , Carcinoma de Células Escamosas do Esôfago , Feminino , Citometria de Fluxo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Fator de Transcrição STAT3/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mol Biol Evol ; 31(9): 2365-75, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24916032

RESUMO

Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.


Assuntos
Antígenos de Diferenciação de Linfócitos T/genética , Biologia Computacional/métodos , Evolução Molecular , Glicoproteínas de Membrana/genética , Animais , Evolução Biológica , Duplicação Gênica , Genoma Humano , Humanos , Família Multigênica , Filogenia , Primatas/genética , Primatas/metabolismo , Seleção Genética , Análise de Sequência de DNA , Especificidade da Espécie
17.
Diagn Pathol ; 9: 98, 2014 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-24886405

RESUMO

BACKGROUND: The radiation resistance of prostate cancer remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of berberine, a commonly used natural product, on the radiosensitivity of prostate cancer. METHODS: Prostate cancer cell line LNCaP and DU-145 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and colony formation, and apoptosis were evaluated. Moreover, LNCaP cells were xenografted into nude mice and subjected to IR and/or berberine treatment. The expression of HIF-1α and VEGF in prostate cancer cells and xenografts was detected by Western blot analysis. RESULTS: Berberine increased radiosensitivity of prostate cancer cells and xenografts in a dose dependent manner, and this was correlated with the inhibition of HIF-1α and VEGF expression. CONCLUSIONS: Berberine may inhibit the expression of HIF-1α and VEGF and thus confer radiosensitivity on prostatic cancer cells. Berberine has potential application as an adjuvant in radiotherapy of prostatic cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1519827543125021.


Assuntos
Berberina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fatores de Tempo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
BMC Genomics ; 15: 305, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24758272

RESUMO

BACKGROUND: With its plumage color dimorphism and unique history in North America, including a recent population expansion and an epizootic of Mycoplasma gallisepticum (MG), the house finch (Haemorhous mexicanus) is a model species for studying sexual selection, plumage coloration and host-parasite interactions. As part of our ongoing efforts to make available genomic resources for this species, here we report a transcriptome assembly derived from genes expressed in spleen. RESULTS: We characterize transcriptomes from two populations with different histories of demography and disease exposure: a recently founded population in the eastern US that has been exposed to MG for over a decade and a native population from the western range that has never been exposed to MG. We utilize this resource to quantify conservation in gene expression in passerine birds over approximately 50 MY by comparing splenic expression profiles for 9,646 house finch transcripts and those from zebra finch and find that less than half of all genes expressed in spleen in either species are expressed in both species. Comparative gene annotations from several vertebrate species suggest that the house finch transcriptomes contain ~15 genes not yet found in previously sequenced vertebrate genomes. The house finch transcriptomes harbour ~85,000 SNPs, ~20,000 of which are non-synonymous. Although not yet validated by biological or technical replication, we identify a set of genes exhibiting differences between populations in gene expression (n = 182; 2% of all transcripts), allele frequencies (76 FST ouliers) and alternative splicing as well as genes with several fixed non-synonymous substitutions; this set includes genes with functions related to double-strand break repair and immune response. CONCLUSIONS: The two house finch spleen transcriptome profiles will add to the increasing data on genome and transcriptome sequence information from natural populations. Differences in splenic expression between house finch and zebra finch imply either significant evolutionary turnover of splenic expression patterns or different physiological states of the individuals examined. The transcriptome resource will enhance the potential to annotate an eventual house finch genome, and the set of gene-based high-quality SNPs will help clarify the genetic underpinnings of host-pathogen interactions and sexual selection.


Assuntos
Processamento Alternativo , Tentilhões/genética , Variação Genética , Transcriptoma , Animais , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Especificidade da Espécie
19.
BMC Med Genomics ; 7: 15, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24646369

RESUMO

BACKGROUND: The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. METHODS: In this study, we exploited whole transcriptome sequencing data from five lung adenocarcinoma tissues and their matched normal tissues to interrogate intron retention, a less studied alternative splicing form which has profound structural and functional consequence by modifying open reading frame or inserting premature stop codons. RESULTS: Abundant intron retention events were found in both tumor and normal tissues, and 2,340 and 1,422 genes only contain tumor-specific retentions and normal-specific retentions, respectively. Combined with gene expression analysis, we showed that genes with tumor-specific retentions tend to be over-expressed in tumors, and the abundance of intron retention within genes is negatively related with gene expression, indicating the action of nonsense mediated decay. Further functional analysis demonstrated that genes with tumor-specific retentions include known lung cancer driver genes and are found enriched in pathways important in carcinogenesis. CONCLUSIONS: We hypothesize that intron retentions and consequent nonsense mediated decay may collectively counteract the over-expression of genes promoting cancer development. Identification of genes with tumor-specific retentions may also help develop targeted therapies.


Assuntos
Adenocarcinoma/genética , Íntrons/genética , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Genes Neoplásicos , Genoma Humano/genética , Humanos , Degradação do RNAm Mediada por Códon sem Sentido/genética , Processamento de RNA/genética
20.
Tumour Biol ; 35(6): 5173-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24515656

RESUMO

Inconsistent results are often found regarding the risk of genetic variants in lung cancer association studies. To alleviate these conflicts, we performed a large-scale meta-analysis to evaluate the effect of variants on lung cancer in East Asian population (Han Chinese, Japanese, and Korean). Forty-three genetic variants with data from at least three independent case-control studies were under investigation of which two variants (rs1800734 in hMLH1, rs2273953-rs1801173 bi-marker in P73) were first meta-analyzed in East Asians. We found that three variants in CYP1A1, GSTM1, and XRCC1 showed consistently significant associations with lung cancer in mixed analysis and stratified analysis, and several variants showed diverse effects interacting with different environmental factors in stratified analysis. Our study presents a comprehensive and systematic analysis of lung cancer association studies in East Asians and confirms the effect of three variants in lung cancer risk. Additionally, result from stratified analysis suggests the importance of inclusion of environmental factors, such as smoking and tumor histology, in the analysis.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Variação Genética , Neoplasias Pulmonares/genética , Estudos de Casos e Controles , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Viés de Publicação , Risco , Fumar/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA