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1.
Chem Biol Interact ; 308: 164-169, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100272

RESUMO

Emerging data indicate that prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could interfere with myogenic differentiation in vivo. Acetylcholinesterase (EC3.1.1.7; AChE), an enzyme critical for cholinergic neurotransmission, is abundantly expressed in neurons and mature myotubes, and we recently found that muscle AChE expression was suppressed in parallel with the inhibition of myogenic differentiation upon TCDD treatment in mouse C2C12 cells. This TCDD-induced suppression of muscle AChE was proposed to involve an aryl hydrocarbon receptor (AhR)-independent mechanism, but the precise underlying mechanism remains unclear. Considering the widely recognized role of muscular activity in AChE expression and its potential crosstalk with the AhR signaling pathway, we sought to investigate the effect of TCDD on muscle AChE expression in the presence of muscular activity. Therefore, we employed a highly contractile rat primary skeletal muscle culture system in which AChE activity and the expression of genes related to it (AChE T subunit and collagen Q (ColQ)) were increased during the myogenic differentiation process. Although TCDD treatment successfully induced the expression of genes regulated by AhR activation, the treatment exerted no notable effects on myogenic differentiation. Moreover, muscle AChE enzymatic activity and mRNA level remained unchanged following TCDD treatment, and only ColQ mRNA expression was slightly increased after 4-day treatment with TCDD (10-10 M). The compensatory role of muscle-contraction-related signaling pathways in this newly identified unresponsiveness of muscle AChE to TCDD warrants further investigation.


Assuntos
Acetilcolinesterase/metabolismo , Diferenciação Celular/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Acetilcolinesterase/genética , Animais , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Contração Muscular/efeitos dos fármacos , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Dibenzodioxinas Policloradas/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
2.
Chem Biol Interact ; 306: 147-151, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31034797

RESUMO

Flavonoids, considered as phytoestrogen mainly deriving from fruit and vegetable, are known to have beneficial effects in brain functions. The role of flavonoids in induction of a cholinergic enzyme, acetylcholinesterase (AChE), was being explored here. In cultured PC12 cells, twenty-four commonly found flavonoids were tested for its induction on AChE activity. Fourteen flavonoids showed induction, and five of them had robust effect, i.e. daidzin, alpinetin, irisflorentin, cardamonin and lysionotin. The induction of AChE was fully blocked by pre-treatment of G15 (a selective G protein-coupled receptor 30 [GPR 30] antagonist), suggesting a direct involvement of a membrane-bound estrogen receptor, named as GPR 30, in the cultures. In addition, daidzin was further identified to induce expression of tetrameric globular form of proline-rich membrane anchor (PRiMA)-linked AChE. In parallel, application of daidzin in cultured PC12 cells significantly induced expression of neurofilaments, markers for neuronal differentiation. Taken together, flavonoids could induce the expression of AChE via GPR 30 in cultured PC12 cells, which could be a good candidate for possible treatment of the brain diseases.


Assuntos
Acetilcolinesterase/genética , Flavonoides/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/metabolismo , Acetilcolinesterase/metabolismo , Animais , Benzodioxóis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/antagonistas & inibidores , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação Enzimológica da Expressão Gênica , Células PC12 , Quinolinas/farmacologia , Ratos , Relação Estrutura-Atividade
3.
Anat Rec (Hoboken) ; 302(6): 931-940, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30737902

RESUMO

Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-ß2 as a downstream target of miR-618. In further research, we identified TGF-ß2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-ß2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-ß2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc.

4.
J Environ Sci (China) ; 76: 368-376, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30528028

RESUMO

Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms are still unclear. During the process of astrocyte reactivation, migration is a critical cellular event. In the present study, we employed wound-healing assay and Transwell® motility assay to explore the effects of TCDD on cell migration in primary cultured rat cortical astrocytes. We found that upon TCDD treatments at relative low concentrations (10-10 and/or 10-9 mol/L), the ability of primary astrocytes to migrate horizontally and vertically was promoted. In line with this cellular effect, the mRNA expression of two pro-migratory genes, including cell division cycle 42 (CDC42) and matrix metalloproteinase 2 (MMP2) was induced by TCDD treatment. Dioxin exerts its toxic effects mainly through aryl hydrocarbon receptor (AhR) pathway. So the role of AhR pathway in the pro-migratory effects of TCDD was examined using an AhR antagonist, CH223191. We found that application of CH223191 significantly reversed the pro-migratory effects of TCDD. Interestingly, the basal ability of horizontal migration as well as basal levels of CDC42 and MMP2 expression were dramatically reduced suggesting a possible physiological role of AhR in maintaining the endogenous migration ability of the primary astrocytes. These findings support the notion that dioxin promotes astrocyte reactivation at molecular and cellular levels.


Assuntos
Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Astrócitos/metabolismo , Células Cultivadas , Ratos , Ratos Sprague-Dawley
5.
IEEE Trans Cybern ; 48(11): 3080-3091, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29990098

RESUMO

To benefit the skin care, this paper aims to design an automatic and effective visual analysis framework, with the expectation of recognizing the skin disease from a given image conveying the disease affected surface. This task is nontrivial, since it is hard to collect sufficient well-labeled samples. To address such problem, we present a novel transfer learning model, which is able to incorporate external knowledge obtained from the rich and relevant Web images contributed by grassroots. In particular, we first construct a target domain by crawling a small set of images from vertical and professional dermatological websites. We then construct a source domain by collecting a large set of skin disease related images from commercial search engines. To reinforce the learning performance in the target domain, we initially build a learning model in the target domain, and then seamlessly leverage the training samples in the source domain to enhance this learning model. The distribution gap between these two domains are bridged by a linear combination of Gaussian kernels. Instead of training models with low-level features, we resort to deep models to learn the succinct, invariant, and high-level image representations. Different from previous efforts that focus on a few types of skin diseases with a small and confidential set of images generated from hospitals, this paper targets at thousands of commonly seen skin diseases with publicly accessible Web images. Hence the proposed model is easily repeatable by other researchers and extendable to other disease types. Extensive experiments on a real-world dataset have demonstrated the superiority of our proposed method over the state-of-the-art competitors.

6.
Environ Sci Technol ; 52(15): 8065-8074, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29995397

RESUMO

Acetylcholinesterase (AChE, EC 3.1.1.7) is a classical biomarker for monitoring contamination and intoxication of organophosphate (OP) and carbamate pesticides. In addition to these classical environmental AChE inhibitors, other organic toxic substances have been found to alter AChE activity in various species. These emerging organic AChE disruptors include certain persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs), and wildly used chemicals, most of which have received considerable public health concern in recent years. It is necessary to re-evaluate the environmental significances of AChE in terms of these toxic substances. Therefore, the present review is aiming to summarize correlations of AChE activity of certain organisms with the level of the contaminants in particular habitats, disruptions of AChE activity upon treatment with the emerging disruptors in vivo and in vitro, and action mechanisms underlying the effects on AChE. Over 40 chemicals belonging to six main categories were reviewed, including 12 POPs listed in the Stockholm Convention. AChE activity in certain organisms has been found to be well correlated with the contamination level of certain persistent pesticides and PAHs in particular habitats. Moreover, it has been documented that most of the listed toxic chemicals could inhibit AChE activity in diverse species ranging from invertebrates to mammals. Besides directly inactivating AChE, the mechanisms in terms of interference with the biosynthesis have been recognized for some emerging AChE disruptors, particularly for dioxins. The collected evidence suggests that AChE could serve as a potential biomarker for a diverse spectrum of organic environmental pollutants.

7.
Environ Pollut ; 235: 965-973, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29751400

RESUMO

Dioxin-induced toxicities that affect the development of the motor system have been proposed since many years. However, cellular evidence and the molecular basis for the effects are limited. In this study, a cultured mouse myoblast cell line, C2C12, was utilized to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on myogenic differentiation and expression of acetylcholinesterase (AChE), a neuromuscular transmission-related gene. The results showed that TCDD exposure at 10-10 M repressed the myotube formation of C2C12 cells by disturbing the fusion process and suppressing the expression of myosin heavy chain, a myobute structural protein, and not by induction of cytotoxicity. Furthermore, TCDD dose dependently suppressed the transcriptional expression and enzymatic activity of AChE during the myogenic differentiation, particularly in the middle stage. However, the administration of aryl hydrocarbon receptor antagonists, CH223191 and alpha-naphthoflavone, did not completely reverse the TCDD-induced downregulation of muscular AChE during myogenic differentiation. These findings suggest that low dose exposure to dioxin may result in disturbances of muscle differentiation and neuromuscular transmission.


Assuntos
Substâncias Perigosas/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Animais , Compostos Azo , Benzoflavonas , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Camundongos , Pirazóis , Receptores de Hidrocarboneto Arílico/metabolismo
8.
Oncol Lett ; 15(4): 5243-5249, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552163

RESUMO

Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the ß-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.

9.
J Environ Sci (China) ; 63: 260-267, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29406108

RESUMO

Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3'-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.


Assuntos
Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Acetilcolinesterase/metabolismo , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Neuroblastoma , Testes de Toxicidade
10.
Oncotarget ; 9(4): 5137-5154, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29435168

RESUMO

In this study, we investigated the role of Fat atypical cadherin 4 (FAT4) in gastric cancer (GC) progression. Immunohistochemical analysis showed lower FAT4 expression in tumor tissues from GC patients than in normal gastric epithelium. Lower FAT4 expression was associated with poor prognosis, tumor size and invasion, and lymph node and distant metastases. Multivariate analysis showed that TNM stage, lymph node and distant metastases, Lauren classification, and FAT4 expression were independent prognostic factors in GC. Methylation-specific PCR analysis showed increased FAT4 promoter methylation in GC tumor tissues and cell lines. Higher FAT4 promoter methylation was associated with low FAT4 expression and a poor prognosis. BGC-823 cells showed increased FAT4 expression upon treatment with 5-azacytidine, demethylating agent. FAT4 knockdown in BGC-823 cells led to increased cell proliferation, migration and invasiveness. Moreover, xenografts of BGC-823 cells with FAT4 knockdown showed enhanced tumor growth and metastasis in nude mice. These findings demonstrate that low FAT4 expression is associated with a poor prognosis in GC patients.

11.
Sci Rep ; 7(1): 10103, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28860601

RESUMO

Emerging evidence has shown that dioxin causes dysregulation of microRNAs (miRs) in a variety of tissues or cells. However, little is known about dioxin effects on neuronal miRs expression. In the present study, 277 differentially expressed miRs were identified by miRs microarray analysis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, at 10-10 M) treated SK-N-SH neuroblastoma cells. Among them, 53 miRs exhibited changes of more than 0.4-fold. Consistent with the microarray data, we verified the induction effect of TCDD on hsa-miR-608 expression, which is a primate-specific miR associated with brain functions. Bioinformatics analysis showed involvement of hsa-miR-608 in cytoskeleton organization, in which one of the hsa-miR-608 target genes, Cell Division Cycle 42 (CDC42), might play a role. We also confirmed induction of CDC42 expression by TCDD in SK-N-SH cells. TCDD induced the expression of CDC42 mRNA in hsa-miR-608 inhibitor transfected cells more obviously than in control cells, suggesting involvement of both transcriptional and post-transcriptional mechanisms in the TCDD-induced CDC42 regulation. Furthermore, CH223191, an antagonist of the aryl hydrocarbon receptor (AhR), counteracted TCDD-induced hsa-miR-608 and CDC42 expression. These results indicated that AhR not only mediates transcriptional induction of CDC42, but also hsa-miR-608-induced post-transcriptional regulation of CDC42 in dioxin treated neuroblastoma cells.

12.
Mol Med Rep ; 16(5): 6882-6889, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901473

RESUMO

Prolyl hydroxylase 3 (PHD3) is widely accepted as a tumor suppressor; however, the expression of PHD3 in various cancer types remains controversial. The present study aimed to investigate the association between PHD3 expression and the clinicopathological features of gastric cancer using reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. The effects of PHD3 in gastric cancer cell lines were assessed using western blot analysis and transwell migration assays. The present results revealed that PHD3 expression was increased in adjacent non­cancerous tissue compared with in gastric cancer tissue, and PHD3 overexpression was correlated with the presence of well­differentiated cancer cells, early cancer stage classification and the absence of lymph node metastasis. In vitro experiments demonstrated that PHD3 may act as a negative regulator of hypoxia­inducible factor­1α and vascular endothelial growth factor, both of which participate in tumor angiogenesis. In conclusion, the present results suggested that PHD3 may act as a tumor suppressor in gastric cancer. Therefore, the targeted regulation of PHD3 may have potential as a novel therapeutic approach for the treatment of patients with gastric cancer.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolil Hidroxilases/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Linhagem Celular , Movimento Celular , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prolil Hidroxilases/química , Prolil Hidroxilases/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Oncol Rep ; 38(1): 100-108, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28560419

RESUMO

This study investigated the effect of miR-101 on proliferation, migration, invasion, and chemotherapy sensitivity in colon cancer cell lines HT-29 and RKO. MicroRNAs are a class of small noncoding RNA molecules, which play important roles in diverse biological processes of human cancers, such as carcinogenesis, development, differentiation, and apoptosis. The expression of miR-101 in colon cancer and adjacent non-tumor tissues were examined by quantitative real-time polymerase chain reaction. The expression of miR-101 was upregulated by recombinant adenovirus Ad-miR-101. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cloning methods. Cell migration and invasion potential were examined using Transwell migration and Matrigel invasion chamber assays. Drug sensitivity to 5-fluorouracil (5-FU) and cisplatin (DDP) was explored using MTT assays and l acridine orange/ethidium bromide double staining. The expression of miR-101 decreased in colon cancer tissues compared with adjacent non-tumor tissues. The upregulated expression of miR-101 suppressed cell proliferation and inhibited cell migration and invasion in HT-29 and RKO colon cancer cell lines. The overexpression of miR-101 promoted the inhibitory effect of 5-FU and DDP on HT-29 cells. The expression of miR-101 was downregulated in colon cancer. The upregulated expression of miR-101 inhibited proliferation and migration, and increased the sensitivity of colon cancer cells to chemotherapy.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Células Tumorais Cultivadas
14.
J Biol Chem ; 292(14): 5676-5684, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28193841

RESUMO

To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here we show that Akirin2 is required for neural development in Xenopus and that knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin. Akirin2 acts antagonistically to Geminin, thus regulating Sox2 expression, and maintains the neural precursor state by participating in the Brg1/Brm-associated factor (BAF) complex mediated by BAF53a. Additionally, Akirin2 also modulates N-tubulin expression by acting upstream of neuronal differentiation 1 (NeuroD) and in parallel with neurogenin-related 1 (Ngnr1) during terminal neuronal differentiation. Thus, our results reveal a novel model in which Akirin2 precisely coordinates and temporally controls Xenopus neural development.


Assuntos
Diferenciação Celular/fisiologia , Neurogênese/fisiologia , Neurônios/metabolismo , Proteínas Repressoras/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Geminina/genética , Geminina/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Proteínas Repressoras/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis
15.
Oncotarget ; 8(1): 1247-1261, 2017 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-27901487

RESUMO

Increased expression of HOXB7 has been reported to correlate with the progression in many cancers. However, the specific mechanism by which it promotes the evolution of gastric cancer (GC) is poorly understood.In this study, we sought to investigate the role of HOXB7 in GC by assessing HOXB7 expression in patient tissue and its correlation to clinical characteristics. We found that GC tissues showed increased expression of HOXB7 and that the HOXB7 expression was significantly associated with Lauren classification, invasion depth, lymphatic metastasis and poor prognosis, and could serve as an independent prognostic factor. To further investigate the role of HOXB7 in GC, we generated stable GC cell lines and both over-expressed and knocked down HOXB7 expression. Over-expression of HOXB7 in GC cell lines enhanced cell proliferation, colony formation, migration and invasion ability, whereas the opposite trends were observed upon reduction of HOXB7 expression by knockdown. These findings were further supported by our in vivo studies which show that HOXB7 expression can affect the GC cells' subcutaneous growth and lung metastases. A Phospho-MAPK Array Kit was used to explore the possible mechanism of HOXB7-induced cell proliferation and invasion. We found that the AKT signaling pathway and the two members of the MAPK pathway, were involved in those promoting effects. In conclusion, our results showed that increased expression of HOXB7 might play an important role in promoting GC proliferation, migration and invasion by inducing both AKT and MAPK pathways, thus resulting in progression of, and poor prognosis in GC patients.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
16.
J Environ Sci (China) ; 62: 92-99, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29289296

RESUMO

Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose (0.1µg/(kg▪bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the differentially expressed genes. And the changes of several picked genes have been verified by real-time PCR. A total of 145 up-regulated and 64 down-regulated genes were identified. The metabolic processes, interleukin-1 secretion and production were significantly associated with the differentially expressed genes. And the genes regulated by dioxin also clustered to cholinergic synapse and long-term potentiation. Candidate biomarker genes such as egr1, gad2, gabrb3, abca1, ccr5 and pycard may be toxicological targets for dioxin. Furthermore, synaptic plasticity and neuro-immune system may be two principal affected areas by dioxin.


Assuntos
Encéfalo/fisiologia , Expressão Gênica/efeitos dos fármacos , Substâncias Perigosas/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Animais , Ratos , Testes de Toxicidade Crônica , Regulação para Cima
17.
Onco Targets Ther ; 9: 6099-6109, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27785057

RESUMO

OBJECTIVES: To examine the expression of ALDOB in gastric cancer (GC) tissue and to reveal its potential clinicopathological and prognostic significance. MATERIALS AND METHODS: We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed. RESULTS: The microarray analysis revealed that ALDOB was downregulated (more than sevenfold) in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC. CONCLUSION: The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC.

18.
Chem Biol Interact ; 259(Pt B): 286-290, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27374124

RESUMO

Acetylcholinesterase (AChE; EC 3.1.1.7) is a vital functional enzyme in cholinergic neurotransmission which can rapidly hydrolyze neurotransmitter, acetylcholine, in the central and peripheral nervous systems. Emerging evidence showed that in addition to classical environmental AChE inhibitors, e.g. organophosphate and carbamate pesticides, dioxins are a new type of xenobiotic causing impairment of AChE. Dioxin can transcriptionally or post-transcriptionally suppress AChE expression in human neuroblastoma cells or mouse immune cells via the aryl hydrocarbon receptor (AhR) pathway, respectively. Dioxins can affect gene expression through other mechanisms, such as cross-talk with other signaling cascades and epigenetic modulations. Therefore, in this review, by summarizing the known mechanisms of AChE regulation and dioxin-induced gene alteration, potential signaling cascades and epigenetic mechanisms are proposed for dioxin-mediated AChE regulation. Mitogen activated protein (MAP) kinase, 3', 5'-cyclic adenosine monophosphate (cAMP) and calcium-related singaling pathways, as well as potential epigenetic mechanisms, such as DNA methylation, and post-transcriptional regulation via microRNAs, including hsa-miR-132, hsa-miR-212 and hsa-miR-25-3p are discussed here. These proposed mechanisms may be invaluable not only to promote comprehensive understanding of the action mechanisms for dioxin, but to illustrate the molecular basis of dioxin-induced health impacts.


Assuntos
Acetilcolinesterase/metabolismo , Dioxinas/toxicidade , Neurônios/enzimologia , Transdução de Sinais/efeitos dos fármacos , Animais , Epigênese Genética/efeitos dos fármacos , Humanos , Neurônios/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo
19.
Onco Targets Ther ; 9: 2305-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27143926

RESUMO

MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial-mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor-node-metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.

20.
IEEE Trans Cybern ; 46(12): 3220-3232, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27046858

RESUMO

Clustering is a useful statistical tool in computer vision and machine learning. It is generally accepted that introducing supervised information brings remarkable performance improvement to clustering. However, assigning accurate labels is expensive when the amount of training data is huge. Existing supervised clustering methods handle this problem by transferring the bag-level labels into the instance-level descriptors. However, the assumption that each bag has a single label limits the application scope seriously. In this paper, we propose weakly supervised multilabel clustering, which allows assigning multiple labels to a bag. Based on this, the instance-level descriptors can be clustered with the guidance of bag-level labels. The key technique is a weakly supervised random forest that infers the model parameters. Thereby, a deterministic annealing strategy is developed to optimize the nonconvex objective function. The proposed algorithm is efficient in both the training and the testing stages. We apply it to three popular computer vision tasks: 1) image clustering; 2) semantic image segmentation; and 3) multiple objects localization. Impressive performance on the state-of-the-art image data sets is achieved in our experiments.

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