Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.679
Filtrar
1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 609-614, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699190

RESUMO

Objective To detect the methylation status of SALL3 gene promoter region in normal cervical tissues,cervical cancer tissues,and cervical cancer cell lines and thus explore the relationship between methylation status and the expression of SALL3 gene.Methods The DNA methylation statuses of SALL3 gene in normal cervical,cervical cancer tissues and cervical cancer cell lines were analyzed by methylation-specific PCR(MS-PCR).The expressions of SALL3 mRNA in cervical cancer cell lines,cervical cancer tissues,and normal cervical tissues were detected by RT-PCR.Results In cervical cancer and matched peri-carcinomatous samples,the methylation levels of SALL3 were up-regulated(CCa vs.CCap:P=0.046;CCa vs.NC P=0.039)and the protein expressions were down-regulated(CCa vs.CCap:P=0.012;CCa vs.NC P=0.000)when compared with normal cervix samples.The mRNA levels of SALL3 in HeLa and SiHa cells treated with 5-Azacytidine were elevated in a dose-dependent manner(HeLa:P=0.001;SiHa:P=0.002).The methylation level of SALL3 was higher in high risk human papillomavirus(HPV)-positive cervical samples than in HPV-negative cervical samples(P=0.014),which also resulted in a descending SALL3 expression in HPV-positive samples(P=0.021).Conclusions The hypermethylation of SALL3 in promoter regions inhibits the expression of SALL3 in cervical cancer tissue samples.Infection with high-risk HPV serotypes may increase the methylation of SALL3 promoter region,silence its expression,and thus promote the development of cervical cancer.


Assuntos
Metilação de DNA , Proteínas de Homeodomínio/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Infecções por Papillomavirus/genética , RNA Mensageiro/genética
2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1095-1101, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512449

RESUMO

Objective: To evaluate the correlation between the Mohawk (MKX) expression level and the collagen fiber diameter of autologous hamstring tendon graft during the stable graft remodeling phase after anterior cruciate ligament (ACL) reconstruction. Methods: Between January 2018 and August 2018, patients who underwent arth-roscopic single-bundle anatomical ACL reconstruction with autologous hamstring tendons for at least 48 months and also underwent second-look arthroscopy were enrolled in study. During the second-look arthroscopic procedures, ACL graft biopsies were performed from the surface of central part of the ligament. MKX expressions of ACL grafts were analysed by real-time fluorescent quantitative PCR (qRT-PCR). The ultrastructure of collagen fibers of grafts were evaluated by transmission electron microscopy, which included average diameter of collagen fibers (D c), average diameter of large-diameter collagen fibers (D L), average diameter of small-diameter collagen fibers (D S), and large-small collagen fibers ratio (R L/S). The correlation between MKX expression level and graft collagen fiber diameter was calculated. Results: Twenty-six patients met the selection criteria and their ACL graft specimens were enrolled in the study. The interval between ACL reconstruction and second-look arthroscopy was 52-128 months, with an average of 78.6 months. Arthroscopic graft remodeling score was 3-6 (mean, 4.8). There were 17 cases of excellent remodeling and 9 cases of fair remodeling. All ACL grafts showed typical bimodal distributions of both large-diameter collagen fibers and small-diameter collagen fibers, but the ultrastructural characteristics of the graft collagen fibers were different according to different remodeling status under arthroscopy. The D C, D L, D S, and R L/S of the graft specimens were (65.2±9.3) nm, (91.6±10.5) nm, (45.7±8.6) nm, and 0.73±0.12, respectively. The relative expression level of MKX was 1.42±0.11, which was positively linearly correlated with D C, D L, and R L/S, and the correlation coefficient was statistically significant ( r=0.809, P=0.000; r=0.861, P=0.000; r=0.942, P=0.000), while there was no significant correlation between D S and relative expression level of MKX ( r=0.147, P=0.238). Regression analysis showed that the relative expression level of MKX could predict the D C, D L, and R L/S results of the ACL graft specimens ( P<0.05). Conclusion: After autologous hamstring tendon grafts stepped into stabilized remodeling phase, MKX expression level could predict the diameter measurement results of collagen fibers and be used as an important evaluation basis for graft collagen anabolic metabolism.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Colágeno , Regulação da Expressão Gênica no Desenvolvimento , Tendões dos Músculos Isquiotibiais , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia , Colágeno/metabolismo , Colágeno/ultraestrutura , Correlação de Dados , Tendões dos Músculos Isquiotibiais/citologia , Tendões dos Músculos Isquiotibiais/metabolismo , Tendões dos Músculos Isquiotibiais/cirurgia , Proteínas de Homeodomínio/genética , Humanos , Transplante Autólogo
3.
Pol J Pathol ; 70(2): 127-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556563

RESUMO

We tested the association between HOXB13 G84E (rs138213197) germline mutation and PC risk in Polish men. DNA from 103 consecutive, newly diagnosed patients hospitalised because of PC and DNA from 103 men: volunteers, healthy at the time of the study. The G84E mutation was genotyped using Sanger sequencing. The HOXB13 G84E germline mutation was detected in 2.9% of PC men (3/103) and not detected in any healthy man. Two mutation carriers originated from two of 25 families fulfilling hereditary prostate cancer criteria (HPC) and one mutation carrier from one family among 78 families without HPC (PC frequency: 8% vs. 1.3%, OR = 6.70, p = 0.13). In two of three mutation carriers, disease was detected above 60 years of age. There was a trend for a lower probability of 5-year survival in patients with G84E than in patients without it (66.7% vs. 94.0%, p = 0.08). The HOXB13 G84E germline mutation is associated with increased prostate cancer risk in Polish men, with hereditary form of the disease, and probably with older age at PC onset (> 60 years of age) and shorter survival. However, it is not associated with PSA level, or PC stage or grade at the time of diagnosis.


Assuntos
Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polônia , Antígeno Prostático Específico/sangue , Fatores de Risco
4.
Gene ; 718: 144048, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421189

RESUMO

Main conclusion Among 247 RsAP2/ERF identified, the majority of the 21 representatives were preferably expressed under drought and heat while suppressed under heavy metals, indicating their potential roles in abiotic stress responses and tolerance. APETALA2/Ethylene-Responsive factor (AP2/ERF) transcription factor (TF) is one of the largest gene families in plants that play a fundamental role in growth and development as well as biotic and/or abiotic stresses responses. Although AP2/ERFs have been extensively characterized in many plant species, little is known about this family in radish, which is an important root vegetable with various medicinal properties. The available genome provides valuable opportunity to identify and characterize the global information on AP2/ERF TFs in radish. In this study, a total of 247 ERF family genes were identified from the radish genome, and sequence alignment and phylogenetic analyses classified the AP2/ERF superfamily into five groups (AP2, ERF, DREB, RAV and soloist). Motif analysis showed that other than AP2/ERF domains, other conserved regions were selectively distributed among different clades in the phylogenetic tree. Chromosome location analysis showed that tandem duplication may result in the expansion of RsAP2/ERF gene family. The RT-qPCR analysis confirmed that a proportion of AP2/ERF genes were preferably expressed under drought and heat stresses, whereas they were suppressed under the ABA and heavy metal stresses. These results provided valuable information for further evolutionary and functional characterization of RsAP2/ERF genes, and contributed to genetic improvement of stress tolerances in radish and other root vegetable crops.


Assuntos
Evolução Molecular , Proteínas de Homeodomínio , Metais Pesados/toxicidade , Família Multigênica , Proteínas Nucleares , Filogenia , Proteínas de Plantas , Raphanus , Estresse Fisiológico/efeitos dos fármacos , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raphanus/genética , Raphanus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Nat Commun ; 10(1): 3407, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431620

RESUMO

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.


Assuntos
Biomarcadores Tumorais/genética , Tumor Carcinoide/genética , Carcinoma de Células Grandes/genética , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Hibridização Genômica Comparativa , Conjuntos de Dados como Assunto , Feminino , Genômica , Proteínas de Homeodomínio/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Prognóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Adulto Jovem
6.
Life Sci ; 232: 116664, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31325426

RESUMO

AIMS: MicroRNAs have been demonstrated to be involved in the development of atherosclerosis. The present study aimed to evaluate the effect of miR-99a-5p and its target gene Homeobox A1 (HOXA1) in atherosclerosis. MAIN METHODS: The biological functions of miR-99a-5p on human aortic smooth muscle cells (ASMCs) were assessed by MTT, wound healing and transwell assays. The target genes of microRNAs were predicted by TargetScan and miRDB. The binding of miR-99a-5p and HOXA1 was confirmed by luciferase reporter assay. In the in vivo study, high-fat diet-induced atherosclerosis model was established in Apolipoprotein E knockout mice. Hematoxylin-eosin (H&E), oil Red O and Masson trichrome staining were performed for determination of atherosclerotic lesion. The levels of miR-99a-5p and HOXA1 mRNA were detected by real-time PCR. HOXA1 and migration-associated protein levels were detected by western blot or immunohistochemistry analysis. KEY FINDINGS: MiR-99a-5p inhibited HOXA1 expression by targeting 3'UTR of HOXA1 mRNA. Enforced HOXA1 significantly promoted the proliferation, migration, and invasion of ASMCs. Furthermore, miR-99a-5p overexpression inhibited the proliferation, migration, and invasion of ASMCs stimulated by HOXA1, whereas miR-99a-5p inhibition reversed the effects of HOXA1 knockdown on these behaviours of ASMCs. In vivo, the specific overexpression of miR-99a-5p significantly abated atherosclerotic lesions formatted, accompanied with a significant down-regulation of HOXA1 mRNA and protein expression levels. SIGNIFICANCE: We demonstrate for first time that miR-99a-5p may serve as a potential inhibitor of the atherosclerosis, and miR-99a-5p plays its role partially through targeting HOXA1.


Assuntos
Aterosclerose/prevenção & controle , Regulação da Expressão Gênica , Genes Homeobox , Proteínas de Homeodomínio/genética , MicroRNAs/fisiologia , Fatores de Transcrição/genética , Regiões 3' não Traduzidas , Animais , Aterosclerose/genética , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Fatores de Transcrição/fisiologia
7.
Nat Commun ; 10(1): 2913, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266935

RESUMO

Mechanistic studies in human cancer have relied heavily on cell lines and mouse models, but are limited by in vitro adaptation and species context issues, respectively. More recent efforts have utilized patient-derived xenografts; however, these are hampered by variable genetic background, inability to study early events, and practical issues with availability/reproducibility. We report here an efficient, reproducible model of T-cell leukemia in which lentiviral transduction of normal human cord blood yields aggressive leukemia that appears indistinguishable from natural disease. We utilize this synthetic model to uncover a role for oncogene-induced HOXB activation which is operative in leukemia cells-of-origin and persists in established tumors where it defines a novel subset of patients distinct from other known genetic subtypes and with poor clinical outcome. We show further that anterior HOXB genes are specifically activated in human T-ALL by an epigenetic mechanism and confer growth advantage in both pre-leukemia cells and established clones.


Assuntos
Proteínas de Homeodomínio/metabolismo , Leucemia/metabolismo , Família Multigênica , Animais , Proliferação de Células , Epigênese Genética , Feminino , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Leucemia/genética , Leucemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Modelos Genéticos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo
8.
Medicine (Baltimore) ; 98(27): e16314, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277174

RESUMO

The Ladybird Homeobox 1 (LBX1) gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). The association between LBX1 gene polymorphisms and AIS has been investigated in several studies. However, these findings have yield contradictory results rather than conclusive evidence.This study is to provide a meta-analysis of the published case-control studies on the association between LBX1 gene polymorphisms and AIS in Asian and Caucasian populations.This meta-analysis conformed to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a literature research on PubMed, Embase, Web of Science, and Cochrane Library until February 10, 2018. We included all case-control or cohort studies about association between LBX1 gene polymorphisms and AIS. The Risk Of Bias In Non-randomised Studies-of Interventions and Critical Appraisal Skills Programme were used to evaluate the risk of bias and study quality. We assessed the strength of association by pooled odds ratios (ORs) and 95% confidence intervals (CIs) in all genetic models under a fixed-effect model or random-effect model. We further performed subgroup analysis by ethnicity and sex. Sensitivity analysis and publication bias were also undertaken.A total of 10 studies (11,411 cases and 26,609 controls) were included in this meta-analysis. The pooled results showed a statistically significant association between LBX1 gene polymorphisms and AIS (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001). For stratified analyses by ethnicity and sex, robust significant associations were detected in Asian and Caucasian populations, and in women and men under all genetic models.T allele of rs11190870 and G alleles of rs625039 and rs11598564 represent risk factors for AIS, but G allele of rs678741 may play a protective role in the occurrence of AIS. Further research is needed to confirm this finding and to understand its implications.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Proteínas de Homeodomínio/genética , Polimorfismo Genético/genética , Escoliose/genética , Fatores de Transcrição/genética , Adolescente , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Razão de Chances , Escoliose/etnologia
9.
BMC Plant Biol ; 19(1): 312, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307379

RESUMO

BACKGROUND: The WOX (WUSCHEL-RELATED HOMEOBOX) gene family encodes a class of transcription factors that are unique to green plants, where they are involved in regulating the development of plant tissues and organs by determining cell fate. Although the importance of the WOX gene is well known, there are few studies describing their functions in cotton. RESULTS: In this study, 32 WOX genes were found in Gossypium hirsutum. Phylogenetic analysis showed that WOX proteins of cotton can be divided into three clades: the ancient, intermediate, and WUS clades. The number of WOX proteins in the WUS clade was greater than the sum of the proteins in the other two clades. Our analysis revealed that 20 GhWOX genes are distributed on 16 cotton chromosomes and that duplication events are likely to have contributed to the expansion of the GhWOX family. All GhWOX genes have introns, and each GhWOX protein contains multiple motifs. RNA-seq data and real-time PCR showed that GhWOX13 gene subfamily is specifically expressed at a high level in cotton fibers. We also identified putative GA, NAA, and BR response elements in the promoter regions of the GhWOX13 genes and GhWOX13 transcripts were significantly induced by GA, NAA, and BR. CONCLUSIONS: Our data provides a useful resource for future studies on the functional roles of cotton WOX genes and shows that the GhWOX13 genes may influence cotton fiber development. Our results also provide an approach for identifying and characterizing WOX protein genes in other species.


Assuntos
Fibra de Algodão , Genes de Plantas , Gossypium/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Filogenia , Reguladores de Crescimento de Planta/fisiologia , Proteínas de Plantas/genética
10.
J Agric Food Chem ; 67(28): 7898-7907, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31282664

RESUMO

This study aimed to explore the effects of silencing HB12 and TT8 genes on protein utilization characteristics of alfalfa. Ground samples of 11 HB12-silenced (HB12i), 5 TT8-silenced (TT8i) and 4 wild type (WT) were incubated in a Daisy II incubator with N15 labeled ammonium sulfate for 0, 4, 8, 12, and 24 h. CP degradation and degradational kinetics, microbial nitrogen fractions, and protein metabolic profiles were determined. Moreover, relationships between protein profiles and FTIR spectral parameters were estimated. Results showed that transgenic alfalfa had lower CP degradation, microbial protein, and total available protein compared with WT, especially for HB12i. In addition, CP degradation and protein metabolic profiles were closely correlated with FTIR spectral parameters and thereby could be predicted from spectral parameters. In conclusion, silencing of HB12 and TT8 genes in alfalfa decreased protein degradational and metabolic profiles, which were predictable with FTIR spectral parameters.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Inativação Gênica , Proteínas de Homeodomínio/genética , Medicago sativa/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rúmen/metabolismo , Ração Animal/análise , Animais , Bactérias/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Bovinos , Digestão , Proteínas de Homeodomínio/metabolismo , Cinética , Medicago sativa/química , Medicago sativa/metabolismo , Proteínas de Plantas/química , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteólise , Rúmen/química , Rúmen/microbiologia
11.
Fish Shellfish Immunol ; 92: 680-689, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271837

RESUMO

The Notch signaling pathway is known to regulate innate immunity by influencing macrophage function and interacting with the Toll-like receptor (TLR) signaling pathway. However, the comprehensive role of the Notch signaling pathway in the innate immune response remains unknown. To assess the function of Notch1a in immunity, we examined the innate immune responses to Vibrio parahaemolyticus strain Vp13 of wild-type (WT) and notch1a-/- zebrafish larvae generated using the clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system. The median lethal dose (LD50) of V. parahaemolyticus was significantly lower in notch1a-/- larvae than in WT larvae 3 days post fertilization (dpf). Transcriptome data analysis revealed 359 significantly differentially expressed genes (DEGs), including 246 significantly down-regulated genes and 113 significantly up-regulated genes, in WT infected groups compared with WT control groups. In contrast, 986 significantly DEGs were found in notch1a-/- infected groups compared with notch1a-/- control groups, of which 82 genes were significantly down-regulated and 904 genes were significantly up-regulated. These DEGs belonged to the tumor necrosis factor (TNF), complement, nuclear factor kappa B (NF-κB), cathepsin, interleukin (IL), chemokine, serpin peptidase inhibitor, matrix metallopeptidase, innate immune cells, pattern recognition receptor (PRR), and other cytokine families. Our results indicate that Notch1a plays roles in inhibiting many immunity-related genes and could comprehensively mediate the innate immune response by regulating TLRs, nucleotide-binding-oligomerization-domain-like receptors (NLRs), lectins, complement, ILs, chemokines, TNF, cathepsin, and serpin. Further studies are required to understand the specific mechanism of Notch1a in innate immunity.


Assuntos
Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Imunidade Inata/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/imunologia , Receptor Notch1/genética , Receptor Notch1/imunologia , Transdução de Sinais/imunologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/imunologia , Peixe-Zebra/genética , Peixe-Zebra/imunologia , Animais , Doenças dos Peixes/imunologia , Vibrioses/imunologia , Vibrioses/veterinária , Vibrio parahaemolyticus/fisiologia
12.
BMC Genomics ; 20(1): 512, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221080

RESUMO

BACKGROUND: Dermal papilla cells (DPCs), the "signaling center" of hair follicle (HF), delicately master continual growth of hair in mammals including cashmere, the fine fiber annually produced by secondary HF embedded in cashmere goat skins. Such unparalleled capacity bases on their exquisite character in instructing the cellular activity of hair-forming keratinocytes via secreting numerous molecular signals. Past studies suggested microRNA (miRNAs) and long non-coding RNAs (lncRNAs) play essential roles in a wide variety of biological process, including HF cycling. However, their roles and related molecular mechanisms in modulating DPCs secretory activities are still poorly understood. RESULTS: Here, we separately cultivated DPCs and their functionally and morphologically distinct dermal fibroblasts (DFs) from cashmere goat skins at anagen. With the advantage of high throughput RNA-seq, we synchronously identified 2540 lncRNAs and 536 miRNAs from two types of cellular samples at 4th passages. Compared with DFs, 1286 mRNAs, 18 lncRNAs, and 42 miRNAs were upregulated, while 1254 mRNAs, 53 lncRNAs and 44 miRNAs were downregulated in DPCs. Through overlapping with mice data, we ultimately defined 25 core signatures of DPCs, including HOXC8 and RSPO1, two crucial activators for hair follicle stem cells (HFSCs). Subsequently, we emphatically investigated the impacts of miRNAs and lncRNAs (cis- and trans- acting) on the genes, indicating that ncRNAs extensively exert negative and positive effects on their expressions. Furthermore, we screened lncRNAs acting as competing endogenous RNAs (ceRNAs) to sponge miRNAs and relief their repressive effects on targeted genes, and constructed related lncRNAs-miRNAs-HOXC8/RSPO1 interactive lines using bioinformatic tools. As a result, XR_310320.3-chi-miR-144-5p-HOXC8, XR_311077.2-novel_624-RSPO1 and others lines appeared, displaying that lncRNAs might serve as ceRNAs to indirectly adjust HFSCs status in hair growth. CONCLUSION: The present study provides an unprecedented inventory of lncRNAs, miRNAs and mRNAs in goat DPCs and DFs. We also exhibit some miRNAs and lncRNAs potentially participate in the modulation of HFSCs activation via delicately adjusting core signatures of DPCs. Our report shines new light on the latent roles and underlying molecular mechanisms of ncRNAs on hair growth.


Assuntos
Cabras/genética , Folículo Piloso/metabolismo , RNA Mensageiro/fisiologia , RNA não Traduzido/fisiologia , Animais , Derme/citologia , Feminino , Fibroblastos/metabolismo , Cabras/metabolismo , Cabelo/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Pele/citologia , Trombospondinas/genética , Transcriptoma
13.
RNA ; 25(9): 1211-1217, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31209064

RESUMO

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common forms of muscular dystrophy. FSHD is caused by aberrant expression of the toxic DUX4 gene in muscle. Detecting endogenous DUX4 in patient tissue using conventional methods can be challenging, due to the low level of DUX4 expression. Therefore, developing simple and trustworthy DUX4 detection methods is an important need in the FSHD field. Here, we describe such a method, which uses the RNAscope assay, an RNA in situ hybridization (ISH) technology. We show that a custom-designed RNAscope assay can detect overexpressed DUX4 mRNA in transfected HEK293 cells and endogenous DUX4 mRNA in FSHD patient-derived myotubes. The RNAscope assay was highly sensitive for tracking reductions in DUX4 mRNA following treatment with our therapeutic mi405 microRNA, suggesting that RNAscope-based DUX4 expression assays could be developed as a prospective outcome measure in therapy trials. This study could set the stage for optimizing and developing a new, rapid RNA ISH-based molecular diagnostic assay for future clinical use in the FSHD field.


Assuntos
Proteínas de Homeodomínio/genética , Hibridização In Situ/métodos , RNA/genética , Linhagem Celular , Perfilação da Expressão Gênica/métodos , Células HEK293 , Humanos , Fibras Musculares Esqueléticas/metabolismo , Distrofia Muscular Facioescapuloumeral/genética , Patologia Molecular/métodos , RNA Mensageiro/genética
14.
Nat Immunol ; 20(7): 890-901, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209400

RESUMO

Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8+ T cells responding to acute and chronic viral infections, we found that progenitor-like CD8+ T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing Tox that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8+ T cells and was required for the programming of progenitor-like CD8+ T cells. Thus, long-term CD8+ T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Análise de Célula Única , Animais , Biomarcadores , Imunoprecipitação da Cromatina , Epigênese Genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Memória Imunológica , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Vírus da Coriomeningite Linfocítica/imunologia , Camundongos , Fatores de Tempo , Transcriptoma
15.
DNA Cell Biol ; 38(7): 678-687, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31188017

RESUMO

Staging and pathological grading systems are convenient, but imperfect predictors of recurrence of head and neck squamous cell carcinoma. Therefore, to identify potential alternative prognostic markers, we investigated the methylation status of the promoter of Sal-like protein 2 (SALL2). SALL2 mRNA expression was absent in 8/9 (88.9%) University of Michigan squamous cell carcinoma cell lines, whereas two nonmalignant cell lines had stable expression. The normalized methylation value of SALL2 in cancer cell lines was significantly higher than in normal cell lines. SALL2 methylation found in 74 of 233 (31.8%) tumor specimens was correlated with the methylation status of both SALL1 and SALL3. SALL2 methylation was not associated with any difference in disease-free survival (DFS). Therefore, the presence of SALL2 methylation was statistically correlated with a decrease in DFS in patients with oral cancer (log-rank test, p = 0.032). Furthermore, it was associated with disease recurrence in 36.2% of oral cancer cases, with an odds ratio of 2.922 (95% confidence interval = 1.198-7.130; p = 0.018) by multivariate Cox proportional hazard regression analysis. This study suggests that cytosine-phosphate- guanosine (CpG) hypermethylation is a likely mechanism of SALL2 inactivation and supports the hypothesis that SALL2 could serve as an important clinical risk assessment.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Neoplasias Bucais/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Fatores de Transcrição/metabolismo
16.
Gastroenterology ; 157(3): 838-850.e6, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31163177

RESUMO

BACKGROUND & AIMS: Little is known about mechanisms of perineural invasion (PNI) by pancreatic ductal adenocarcinomas (PDAs) or other tumors. Annexin A2 (ANXA2) regulates secretion of SEMA3D, an axon guidance molecule, which binds and activates the receptor PLXND1 to promote PDA invasion and metastasis. We investigated whether axon guidance molecules promote PNI and metastasis by PDA cells in mice. METHODS: We performed studies in a dorsal root ganglion (DRG) invasion system, wild-type C57BL/6 mice (controls), mice with peripheral sensory neuron-specific disruption of PlxnD1 (PLAC mice), LSL-KRASG12D/+;LSL-TP53R172H/+;PDX-1-CRE+/+ (KPC) mice, and KPC mice crossed with ANXA2-knockout mice (KPCA mice). PDA cells were isolated from KPC mice and DRG cells were isolated from control mice. Levels of SEMA3D or ANXA2 were knocked down in PDA cells with small hairpin and interfering RNAs and cells were analyzed by immunoblots in migration assays, with DRGs and with or without antibodies against PLXND1. PDA cells were injected into the pancreas of control and PLAC mice, growth of tumors was assessed, and tumor samples were analyzed by histology. DRG cells were incubated with SEMA3D and analyzed by live imaging. We measured levels of SEMA3D and PLXND1 in PDA specimens from patients with PNI and calculated distances between tumor cells and nerves. RESULTS: DRG cells increase the migration of PDC cells in invasion assays; knockdown of SEMA3D in PDA cells or antibody blockade of PLXND1 on DRG cells reduced this invasive activity. In mice, orthotopic tumors grown from PDA cells with knockdown of SEMA3D, and in PLAC mice, orthotopic tumors grown from PDA cells, had reduced innervation and formed fewer metastases than orthotopic tumors grown from PDA cells in control mice. Increased levels of SEMA3D and PLXND1 in human PDA specimens associated with PNI. CONCLUSIONS: DRG cells increase the migratory and invasive activities of pancreatic cancer cells, via secretion of SEMA3D by pancreatic cells and activation of PLXND1 on DRGs. Knockdown of SEMA3D and loss of neural PLXND1 reduces innervation of orthotopic PDAs and metastasis in mice. Increased levels of SEMA3D and PLXND1 in human PDA specimens associated with PNI. Strategies to disrupt the axon guidance pathway mediated by SEMA3D and PLXND1 might be developed to slow progression of PDA.


Assuntos
Anexina A2/metabolismo , Orientação de Axônios , Carcinoma Ductal Pancreático/metabolismo , Movimento Celular , Gânglios Espinais/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Pancreáticas/metabolismo , Semaforinas/metabolismo , Animais , Anexina A2/deficiência , Anexina A2/genética , Orientação de Axônios/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/secundário , Comunicação Celular , Gânglios Espinais/patologia , Regulação Neoplásica da Expressão Gênica , Genes p53 , Genes ras , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Humanos , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Invasividade Neoplásica , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Crescimento Neuronal , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fenótipo , Semaforinas/genética , Transdução de Sinais , Transativadores/genética , Células Tumorais Cultivadas
17.
Plant Physiol Biochem ; 141: 250-258, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195255

RESUMO

The homeodomain-leucine zipper (HD-Zip) gene family plays an important role in plant growth and environmental responses. At present, research on the HD-Zip gene family of barley is incomplete. In this study, 32 HD-Zip genes (HvHD-Zip 1-32) were identified from the barley genome and were subsequently divided into four subfamilies according to conserved structure and motif analysis. Whole genome replication events in barley and Arabidopsis, rice, and wheat HD-Zip gene families were analyzed, yielding 3, 14 and 25 gene pairs, respectively, but no segmental or tandem duplication events were identified in the barley HD-Zip gene family. Subsequently, quantitative real-time PCR (qRT-PCR) analysis revealed that the HvHD-Zip gene is sensitive to drought stress and that members of the HD-Zip I and HD-Zip IV subfamilies are generally more sensitive to abiotic stresses. Our results suggest a relationship between barley resistance and the potential key HvHD-Zip gene, which lay the foundation for further functional studies.


Assuntos
Hordeum/genética , Família Multigênica , Estresse Fisiológico , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Biologia Computacional , Duplicação Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma , Genoma de Planta , Proteínas de Homeodomínio/genética , Oryza/genética , Filogenia , Domínios Proteicos , Triticum/genética
18.
Int J Mol Sci ; 20(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31197108

RESUMO

Brn3b (Pou4f2) is a class-4 POU domain transcription factor known to play central roles in the development of different neuronal populations of the Central Nervous System, including retinal ganglion cells (RGCs), the neurons that connect the retina with the visual centers of the brain. Here, we have used CRISPR-based genetic engineering to generate a Brn3b-mCherry reporter mouse without altering the endogenous expression of Brn3b. In our mouse line, mCherry faithfully recapitulates normal Brn3b expression in the retina, the optic tracts, the midbrain tectum, and the trigeminal ganglia. The high sensitivity of mCherry also revealed novel expression of Brn3b in the neuroectodermal cells of the optic stalk during early stages of eye development. Importantly, the fluorescent intensity of Brn3b-mCherry in our reporter mice allows for noninvasive live imaging of RGCs using Scanning Laser Ophthalmoscopy (SLO), providing a novel tool for longitudinal monitoring of RGCs.


Assuntos
Proteínas de Homeodomínio/genética , Proteínas Luminescentes/metabolismo , Retina/metabolismo , Fator de Transcrição Brn-3B/genética , Animais , Sistemas CRISPR-Cas , Genes Reporter , Proteínas de Homeodomínio/metabolismo , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Retina/diagnóstico por imagem , Fator de Transcrição Brn-3B/metabolismo , Vias Visuais/diagnóstico por imagem , Vias Visuais/metabolismo
19.
Medicine (Baltimore) ; 98(23): e15953, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169720

RESUMO

BACKGROUND: Studies showed the controversial results about the effect of common genetic polymorphisms on the atrial fibrillation (AF) recurrence. We performed the systematic review and meta-analysis to qualify the association between common genetic polymorphisms and AF recurrence. METHODS: Articles were systematically retrieved PubMed, Web of Science, EMBASE, Wanfang, and CNKI database and 9 studies including 3204 patients were enrolled in our meta-analysis. RESULTS: Results showed that the associations were significant under rs2200733 3 genetic models (TT vs CC: odds ratio [OR] [confidence interval [CI]] = 1.336 [1.061-1.683], P = .014; CT vs CC: OR [CI] = 0.759 [0.614-0.937], P = .01; TT vs CT + CC: OR [CI] = 2.308 [1.440-3.700], P = .001). The association was significant under rs10033464 genetic model (TT vs GG: OR [CI] = 1.517 [1.165-1.976], P = .002). CONCLUSIONS: Rs13376333 on chromosome 1q21 (in KCNN3), rs7193343 and rs2106261 on chromosome 16q22 (in ZFHX3) were not associated with AF recurrence in our meta-analysis. In total, our meta-analysis found that rs2200733 and rs10033464 on chromosome 4q25 (near PITX2) were associated with the risk of AF recurrence.


Assuntos
Fibrilação Atrial/genética , Cromossomos Humanos/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Recidiva , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Fatores de Transcrição/genética
20.
J Exp Clin Cancer Res ; 38(1): 237, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171015

RESUMO

BACKGROUND: Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC. METHODS: A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced. RESULTS: LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway. CONCLUSION: This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.


Assuntos
Molécula 1 de Adesão Celular/genética , Transformação Celular Neoplásica/genética , Metilação de DNA , Proteínas de Homeodomínio/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Modelos Biológicos , Células-Tronco Neoplásicas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA