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1.
Artigo em Inglês | MEDLINE | ID: mdl-32034805

RESUMO

The aim of this study was to estimate if methotrexate (MTX) promotes cognitive impairment via increased ER stress and disrupted H2 S signaling in the hippocampus, and if H2 S may alleviate MTX-induced cognitive impairment by inhibiting ER stress through CHOP and caspase-12. Cognitive impairment behaviors were observed by Morris Water Maze test and the apoptosis of neurons were assessed by TUNEL assay. The production of neurons was analyzed by DCX and Ki67 immunohistochemistry. The expressions of CHOP and caspase-12 in the hippocampus were determined by Western blot and immunohistochemistry. MTX increased the expression of CHOP and caspase-12 and the number of TUNEL positive cells in the hippocampus by inhibiting endogenous H2 S-induced neuronal pyknosis in the hippocampal DG region. MTX decreased the number of DCX and Ki67 positive cells in the hippocampus in the hippocampal DG region. The results of Morris water maze showed that MTX could damage the spatial memory of rats. The changes of MTX-induced Morris water maze test in mice and H2 S levels in serum and hippocampus, as well as the expression of CHOP and caspase-12 and the number of CHOP and caspase-12 positive neurons in the hippocampus, indicated that H2 S could alleviate the cognitive impairment induced by methotrexate through CHOP and caspase-12.

2.
Onco Targets Ther ; 12: 9827-9848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819482

RESUMO

Introduction: MIR22HG has a reported involvement in the tumorigenesis of a variety of cancers, including hepatocellular carcinoma (HCC). However, the exact molecular mechanism of MIR22HG in HCC has not been clarified. Methods: In the present study, we integrated data from in-house RT-qPCR, RNA-sequencing, microarray, and literature studies to conduct a comprehensive evaluation of the clinico-pathological and prognostic significance of MIR22HG in an extremely large group of HCC samples. We also explored the potential mechanism of MIR22HG in HCC by analyzing the alteration profiles of MIR22HG in HCC to predict transcription factors (TFs) that may interact with MIR22HG and to annotate the biological functions of genes co-expressed with MIR22HG. MIR22HG expression was also compared in HCC nude mice xenografts before and after a treatment with nitidine chloride. Results: We found that MIR22HG was downregulated in HCC and that this downregulation correlated with the malignant phenotype of HCC. Comprehensive analysis of the prognostic impact of MIR22HG in HCC revealed a beneficial effect of MIR22HG on the survival outcome of HCC patients. Seven cases of MIR22HG deep deletion occurred in 360 of the cancer genome atlas (TCGA) provisional HCC samples. A total of 22 MIR22HG-TF-mRNA triplets in HCC were predicted by the lncRNAmap. Co-expressed genes of MIR22HG, identified by weighted correlation network analysis (WGCNA), mainly participated in the pathways involving osteoclast differentiation, chemokine signaling pathways, and hematopoietic cell lineage. In vivo experiments demonstrated that nitidine chloride could stimulate MIR22HG expression in HCC xenografts. Conclusion: In summary, MIR22HG may play a tumor-suppressive role in HCC by coordinating with predicted TFs and co-expressed genes, such as NLRP3, CSF1R, SIGLEC10, and ZEB2, or by being controlled by nitidine chloride.

3.
Oncol Rep ; 42(1): 115-130, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180554

RESUMO

Borax is a boron compound that is becoming widely recognized for its biological effects, including lipid peroxidation, cytotoxicity, genotoxicity, antioxidant activity and potential therapeutic benefits. However, it remains unknown whether exposure of human liver cancer (HepG2) cells to borax affects the gene expression of these cells. HepG2 cells were treated with 4 mM borax for either 2 or 24 h. Gene expression analysis was performed using Affymetrix GeneChip Human Gene 2.0 ST Arrays, which was followed by gene ontology analysis and pathway analysis. The clustering result was validated using reverse transcription­quantitative polymerase chain reaction. A cell proliferation assay was performed using Celigo Image Cytometer Instrumentation. Following this, 2­ or 24­h exposure to borax significantly altered the expression level of a number of genes in HepG2 cells, specifically 530 genes (384 upregulated and 146 downregulated) or 1,763 genes (1,044 upregulated and 719 downregulated) compared with the control group, respectively (≥2­fold; P<0.05). Twenty downregulated genes were abundantly expressed in HepG2 cells under normal conditions. Furthermore, the growth of HepG2 cells was inhibited through the downregulation of PRUNE1, NBPF1, PPcaspase­1, UPF2 and MBTPS1 (≥1.5­fold, P<0.05). The dysregulated genes potentially serve important roles in various biological processes, including the inflammation response, stress response, cellular growth, proliferation, apoptosis and tumorigenesis/oncolysis.


Assuntos
Boratos/farmacologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/genética , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Análise de Sequência com Séries de Oligonucleotídeos
4.
Curr Med Sci ; 39(3): 455-462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209819

RESUMO

Myopia is the leading cause of visual impairments worldwide. Some studies revealed that visual experience in early life affected the final myopia, indicating that environmental factors play an impellent role in the development of myopia. However, risk factors of myopia are still not identified among adolescents in China. A total of 4104 cases of myopia symptom and 3306 emmetropia controls were selected from students in primary and middle schools in Wuhan in 2008. We identified the risk factors associated with myopia symptom by multivariate logistic regression in this cross-sectional study and constructed a risk score system for myopia symptom. The value of the area under the receiver operating characteristic curve (ROC) was 0.735. Furthermore, we followed up 93 students aged 7-9 years for one year and calculated the total points using the score system. We found no significant difference between the final myopia symptom and the results predicted by the total points by pair chi-square test (P>0.05). The score system had a modest ability to estimate the risk factors of myopia symptom. Using this score system, we could identify the students who are at risk of myopia symptom in the future according to their behaviors and environmental factors, and take measures to slow the progress of myopia symptom.


Assuntos
Miopia/diagnóstico , Miopia/epidemiologia , Adolescente , Área Sob a Curva , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Miopia/fisiopatologia , Prognóstico , Curva ROC , Projetos de Pesquisa , Fatores de Risco , Instituições Acadêmicas , Estudantes , Adulto Jovem
5.
Biol Res ; 52(1): 18, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944041

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have emerged as the critical modulators of the tumorigenesis and tumor progression. METHODS: The levels of miR-663 in ovarian cancer cell lines and clinical tissues were detected using qRT-PCR assays. The Transwell invasion and wound healing assay were conducted to assess the roles of miR-663 in the migration and invasion of ovarian cancer cell in vitro. Rescue assays were carried out to confirm the contribution of tumor suppressor candidate 2 (TUSC2) in the aggressiveness of cancer cell which was regulated by miR-663. RESULTS: The levels of miR-663 were up-regulated in ovarian cancer tissues in comparison with the corresponding normal tissues. Up-regulation of miR-663 increased the proliferation, colony formation, migration and invasion of ovarian cancer SKOV3 cell. Additional, over-expression of miR-663 increased the tumor growth of SKOV3 in xenograft model. Bioinformatics analysis and luciferase reporter assay identified that miR-663 decreased the level of TUSC2 via binding to the 3'-UTR of TUSC2 gene. Finally, the expression of TUSC2 was inversely associated with the level of miR-663 in ovarian carcinoma tissue and over-expression of TUSC2 inhibited the migration and invasion abilities of SKOV3 that was promoted by miR-663. CONCLUSION: Altogether, these results indicate that miR-663 acts as a potential tumor-promoting miRNA through targeting TUSC2 in ovarian cancer.


Assuntos
MicroRNAs/genética , Neoplasias Ovarianas/patologia , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Proteínas Supressoras de Tumor/genética
6.
Graefes Arch Clin Exp Ophthalmol ; 257(5): 1045-1053, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903312

RESUMO

PURPOSE: To produce a clinical model for the prediction of myopia development based on the creation of percentile curves of axial length in school-aged children from Wuhan in central China. METHODS: Data of 12,554 children (6054 girls and 6500 boys) were collected and analyzed for the generation of the axial length growth curves. A second data set with 226 children and three yearly successive measurements was used to verify the predictive power of the axial length growth percentile curves. Percentile curves were calculated for both gender groups and four age groups (6, 9, 12, and 15 years). The second data set was used to verify the efficacy of identifying the refractive error of the children using the axial length curves, based on their spherical refractive error from the third visit. RESULTS: From 6 to 15 years of age, all percentiles showed a growth trend in axial length, except for the percentiles below the first quartile, which appear to stabilize after the age of 12 (- 0.10; 95%CI, - 0.36-0.16; P = 0.23 for girls; - 0.16; 95%CI, - 0.70-0.39; P = 0.34 for boys); however, the growth continued for the remaining 75% of cases. The second data set showed that the likelihood of suffering high myopia (spherical refractive error ≤- 5.00D) during adolescent years increased when axial length values were above the first quartile, for both genders. CONCLUSIONS: The data from the current study provide a tool to observe the annual growth rates of axial length and can be considered as an approach to predict the refractive development at school ages.


Assuntos
Comprimento Axial do Olho/crescimento & desenvolvimento , Monitorização Fisiológica/métodos , Miopia/fisiopatologia , Refração Ocular/fisiologia , Adolescente , Criança , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Miopia/epidemiologia , Testes Visuais
7.
Biol. Res ; 52: 18, 2019. graf
Artigo em Inglês | LILACS-Express | ID: biblio-1011420

RESUMO

Abstract Background: MicroRNAs (miRNAs) have emerged as the critical modulators of the tumorigenesis and tumor progression. Methods: The levels of miR-663 in ovarian cancer cell lines and clinical tissues were detected using qRT-PCR assays. The Transwell invasion and wound healing assay were conducted to assess the roles of miR-663 in the migration and invasion of ovarian cancer cell in vitro. Rescue assays were carried out to confirm the contribution of tumor suppressor candidate 2 (TUSC2) in the aggressiveness of cancer cell which was regulated by miR-663. Results: The levels of miR-663 were up-regulated in ovarian cancer tissues in comparison with the corresponding normal tissues. Up-regulation of miR-663 increased the proliferation, colony formation, migration and invasion of ovarian cancer SKOV3 cell. Additional, over-expression of miR-663 increased the tumor growth of SKOV3 in xenograft model. Bioinformatics analysis and luciferase reporter assay identified that miR-663 decreased the level of TUSC2 via binding to the 3'-UTR of TUSC2 gene. Finally, the expression of TUSC2 was inversely associated with the level of miR-663 in ovarian carcinoma tissue and over-expression of TUSC2 inhibited the migration and invasion abilities of SKOV3 that was promoted by miR-663. Conclusion: Altogether, these results indicate that miR-663 acts as a potential tumor-promoting miRNA through targeting TUSC2 in ovarian cancer.

8.
Am J Hematol ; 93(12): 1467-1473, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30160789

RESUMO

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.


Assuntos
Trióxido de Arsênio/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Adolescente , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Lactente , Tempo de Internação , Masculino , Resultado do Tratamento , Tretinoína/uso terapêutico
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(2): 179-182, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29737056

RESUMO

OBJECTIVE: To investigate the correlation of disease activity and thyroid indicators ,immunologic markers of system lupus erythematosus (SLE) in SLE with Hashimoto's thyroiditis (HT). METHODS: The clinical data of 63 cases of SLE with HT were collected. According to Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2000),we classified the patients into four groups,which were remission group (5 cases),low (19 cases),moderate (12 cases) and high (27 cases) disease activity group. Each patient received the measurement of thyroid function indicators and autoantibodies,SLE immunologic indicators,serum complement (C3,C4),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR), and routine blood test. The correlation of thyroid indicators,immunologic markers and disease activity were analyzed. RESULTS: The difference of free triiodothyronine (FT3) level in the four groups was statistically significant (P<0.05),and FT3 was negatively correlated with SLE disease activity (P=0.007) . There was no significant difference in other thyroid indicators and autoantibodies between the different groups (P>0.05). Negative correlation was found between FT3 level and anti-double-stranded DNA (dsDNA),level of anti-La antibody (SSB) and thyroid stimulating hormone (TSH) or thyroid peroxidase antibody (TPOAb). Thyroglobulin autoantibody (TgAb) was negatively related with C4,and positive correlation between FT3 and C3,FT4 and C4,TgAb and IgA. CONCLUSION: The pathogenesis of HT is associated with the disease activity in the patients of SLE with HT.


Assuntos
Autoanticorpos/sangue , Doença de Hashimoto/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Anticorpos Antinucleares/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Proteínas do Sistema Complemento/análise , Doença de Hashimoto/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Glândula Tireoide/fisiopatologia , Tireotropina/sangue
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(2): 183-187, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29737057

RESUMO

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.


Assuntos
Hepatite Autoimune/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Anticorpos Antinucleares/sangue , Feminino , Hepatite Autoimune/complicações , Humanos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações
11.
Cancer Manag Res ; 10: 873-885, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29731667

RESUMO

Purpose: Liver cancer stem cells (CSCs) are known to be associated with the development, survival, proliferation, metastasis, and recurrence of liver tumors. The aim of this study was to investigate the association of liver-enriched activator protein 1 (LAP1) with hepatocellular carcinoma (HCC) and liver CSCs (LCSCs) and explore the impact of LAP1 on LCSCs. Materials and methods: Differences in LAP1 expression in liver cancer tissues versus matched para-tumoral liver tissues and LCSCs versus non-CSCs were analyzed by Western blotting, real-time polymerase chain reaction, immunohistochemistry, and flow cytometry. The effect of LAP1 on liver cancer cells was evaluated by the expression of CSC markers, oncosphere formation, proliferation, migration, and invasion in vitro. Cell cycle distribution and the number of apoptotic cells were analyzed to assess cell cycle and cell apoptosis. Furthermore, a mouse subcutaneous tumor implant model was established to explore the role of LAP1 in the development of HCC in vivo. Finally, the expression of CSC markers in paraffin-embedded sections was evaluated by immunofluorescence. Results: LAP1 was weakly expressed in HCC tumors and cell lines and even weaker in LCSCs. LAP1 inhibited the expression of stem cell-associated genes and reduced the abilities of oncosphere formation, proliferation, migration, and invasion in vitro. Cell cycle assay revealed that LAP1 induced G1/G0 arrest. Furthermore, LAP1 decreased subcutaneous tumor-formation ability and the expression of CSC markers and Ki67 in vivo. Conclusion: LAP1 suppressed the stem cell features of HCC, indicating that it possessed an antitumor effect in liver cancer, both in vitro and in vivo; therefore, LAP1 may prove to be a potential target in liver CSC-targeted therapy.

12.
Int J Mol Med ; 41(5): 2813-2831, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29484429

RESUMO

Mounting evidence has shown that miR-23b-3p, which is associated with cell proliferation, invasion, and apoptosis, acts as a biomarker for diagnosis and outcomes in numerous cancers. However, the clinicopathological implication of miR-23b-3p in hepatocellular carcinoma (HCC) remains unclear. Our study evaluated the role of miR-23b-3p in HCC and investigated its potential application as a marker for preliminary diagnosis and therapy in HCC. High-throughput data from the NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were collected and analyzed. One hundred and one tissue sections of HCC were paired with adjacent non-cancerous HCC as further supplements. miR-23b-3p expression was detected using quantitative real-time PCR. Additionally, the relationship between miR-23b-3p expression and HCC progression and Time-to-recurrence (months) was explored. Ten algorithms were applied to predict the prospective target genes of miR-23b-3p. Next, we conducted bioinformatics analysis for further study. miR-23b-3p expression was pronouncedly decreased in HCC tissues in contrast with their paired adjacent non-cancerous HCC (P<0.001) with RT-qPCR. In total, 405 targets, acquired with consistent prediction from at least five databases, were used for the bioinformatics analysis. According to the Gene Ontology (GO) analysis, all targets were classified into biological processes, cellular components and molecular functions. In the pathway analysis, targets of miR-23b-3p were primarily enriched in the signaling pathways of renal cell carcinoma, hepatitis B and pancreatic cancer (corrected P-value <0.05). In the protein-protein interaction (PPI) network for miR-23b-3p, a total of 8 targets, including SRC, AKT1, EGFR, CTNNB1, BCL2, SMAD3, PTEN and KDM6A, were located in the key nodes with high degree (>35). In conclusion, this study provides impressive illumination of the potential role of miR-23b-3p in HCC tumorigenesis and progression. Furthermore, miR-23b-3p may act as a predictor of HCC and could be a new treatment target.


Assuntos
Carcinoma Hepatocelular/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Redes Reguladoras de Genes , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma
13.
PhytoKeys ; (94): 107-116, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416425

RESUMO

Primulina malipoensis, a new species from limestone areas around the Sino-Vietnamese border, is described and illustrated. This new species is morphologically similar to P. maguanensis and P. lungzhouensis, but obviously differs from the latter two species by its pale greenish-yellow flowers (vs. purple, with different colour patterns). The phylogenetic affinity, illustration and photographs of this new species are provided in this paper.

14.
Artigo em Inglês | MEDLINE | ID: mdl-28804504

RESUMO

OBJECTIVES: To identify the efficacy of auricular acupressure on pain and disability for chronic LBP by systematic review. METHODS: A search of randomized controlled trials was conducted in four English medical electronic databases and three Chinese databases. Two reviewers independently retrieved related studies, assessed the methodological quality, and extracted data with a standardized data form. Meta-analyses were performed using all time-points meta-analysis. RESULTS: A total of 7 trials met the inclusion criteria, of which 4 had the low risk of bias. The findings of this study showed that, for the immediate effect, auricular acupressure had large, significant effects in improving pain within 12 weeks. As for the follow-up effect, the pooled estimates also showed promising effect at 4-week follow-up after 4-week intervention (standardized mean difference = -1.13, 95% CI (-1.70, -0.56), P < 0.001). But, for the disability level, the therapeutic effect was not significant (mean difference = -1.99, 95% CI (-4.93, 0.95), P = 0.18). No serious adverse effects were recorded. CONCLUSIONS: The encouraging evidence of this study indicates that it is recommended to provide auricular acupressure to patients with chronic low back pain. However, a more accurate estimate of the effect will require further rigorously designed large-scale RCTs on chronic LBP for improving pain and disability.

15.
Med Sci Monit ; 23: 2453-2464, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28533502

RESUMO

BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis. RESULTS MiR-375 expression was significantly higher in LUAD by TCGA data compared to normal lung tissue (p<0.0001). In addition, a common pattern of upregulation for miR-375 in LUAD was found in our review of the literature. A total of 682 genes, both LUAD-related and miR-375-related, were obtained from the analytical integration. Critical pathways were unveiled in the network analysis of the overlaps, such as pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and starch and sucrose metabolism. Furthermore, we identified covert miR-375 associated genes that might participate in LUAD by network analysis, such as FGF2 (fibroblast growth factor 2), PAX6 (paired box 6), and RHOJ. The expression of these three genes were all downregulated in LUAD. Finally, FGF2 was revealed to be negatively correlated with miR-375 in LUAD (r=-0.1821, p=0.0001). CONCLUSIONS Overall, our study provides evidence that miR-375 is essential for the progression of LUAD.


Assuntos
Adenocarcinoma/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Adenocarcinoma de Pulmão , Estudos de Coortes , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Pulmão/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Mapas de Interação de Proteínas/genética
16.
Front Immunol ; 8: 320, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28382040

RESUMO

The mechanisms by which tumor-responsive CD8+ T cells are regulated are important for understanding the tumor immunity and for developing new therapeutic strategies. In current study, we identified the expression of 1810011o10 Rik, which is the homolog of human thyroid cancer 1, in intratumoral activated CD8+ T cells in a murine hepatocellular carcinoma (HCC) implantation model. To investigate the role of 1810011o10 Rik in the regulation of antitumor activity of CD8+ T cells, normal CD8+ T cells were transduced with 1810011o10 Rik-expressing lentiviruses. Although 1810011o10 Rik overexpression did not influence agonistic antibody-induced CD8+ T cell activation in vitro, it inhibited the cytotoxic efficacy of CD8+ T cells on HCC cells in vivo. 1810011o10 Rik overexpression impeded CD8+ T cell-mediated HCC cell apoptosis and favored tumor cell growth in vivo. Further investigation revealed that 1810011o10 Rik blocked the nuclear translocation of Notch2 intracellular domain, which is crucial for CD8+ T cell activity. Furthermore, a brief in vitro experiment suggested that both antigen-presenting cells and TGF-ß might be necessary for the upregulation of Rik expression in activated CD8+ T cells. In general, our study disclosed a novel mechanism underlying the negative regulation of antitumor CD8+ T cells during HCC progression.

17.
Pathol Res Pract ; 213(4): 364-372, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28214218

RESUMO

BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Furthermore, bioinformatics analysis was performed to explore the biological role of miR-375 in LUSC. RESULTS: The expression of miR-375 was remarkably reduced in LUSC tissues compared with that in paired lung tissues by qRT-PCR (P=0.003). Additionally, the TCGA dataset suggested that miR-375 was significantly downregulated in 478 LUSC tissues compared with 45 normal lung tissues (P<0.0001), as well as the result derived from GEO datasets (the pooled SMD=-1.01; 95%CIs-1.66 to -0.33, P=0.004). Furthermore, a total of 1348 miR-375-related differently expressed genes were identified by the analytical integration, which were involved in critical pathways of LUSC like neuron differentiation, plasma membrane part and sequence-specific DNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination also unveiled the involvement of target genes in morphine addiction and drug metabolism- other enzymes and neuroactive ligand-receptor interaction. Finally, the expression of WNT5A was inversely correlated with miR-375 expression according to TCGA dataset (r=-0.2342, P<0.0001). CONCLUSIONS: miR-375 exerts a strong tumor-suppressive effect in LUSC and provided novel insight into the biological function in tumorigenesis and progression of LUSC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Transdução de Sinais/genética , Adulto , Idoso , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma
18.
Cell Mol Neurobiol ; 37(4): 595-606, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27324798

RESUMO

One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT3 receptor in the development of PTSD, even though 5-HT3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.


Assuntos
Autofagia , Extinção Psicológica , Medo , Hipocampo/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Animais , Autofagia/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT3 de Serotonina/farmacologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/fisiopatologia
19.
Cancer Cell Int ; 16: 76, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27708550

RESUMO

OBJECTIVE: To explore the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and the clinicopathological features in HCC as well as its biological function. METHODS: Totally, 412 liver tissues were collected, including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor tissues, 37 cirrhosis and 33 normal liver tissues. The expression of TRAF6 was assessed by immunohistochemistry. Then, analysis of the correlations between TRAF6 expression and clinicopathological parameters in HCC was conducted. Furtherer, in vitro experiments on HepG2 and Hep3B cells were performed to validate the biological function of TRAF6 on HCC cells. TRAF6 siRNA was transfected into HepG2 and Hep3B cell lines and TRAF6 expression was evaluated with RT-qPCR and western blot. The assays of cell viability, proliferation, apoptosis and caspase-3/7 activity were carried out to investigate the effects of TRAF6 on HCC cells with RNA interference. Cell viability was assessed with Cell Titer-Blue kit. Cell proliferation was tested with MTS kit. Cell apoptosis was checked through morphologic detection with fluorescence microscope, as well as caspase-3/7 activity was measured with fluorogenic substrate detection. RESULTS: The positive expression rate of TRAF6 protein was 49.7 % in HCC, significantly higher than that of normal liver (12.1 %), cirrhosis (21.6 %) and adjacent non-cancerous tissues (36.3 %, all P < 0.05). Upregulated TRAF6 was detected in groups with metastasis (Z = -2.058, P = 0.04) and with low micro-vessel density (MVD) expression (Z = -2.813, P = 0.005). Spearman correlation analysis further showed that the expression of TRAF6 was positively correlated with distant metastasis (r = 0.158, P = 0.039) and negatively associated with MVD (r = -0.249, P = 0.004). Besides, knock-down of TRAF6 mRNA in HCC cell lines HepG2 and Hep3B both resulted in cell viability and proliferation inhibition, also cell apoptosis induction and caspase-3/7 activity activation. CONCLUSIONS: TRAF6 may contribute to metastasis and deterioration of the HCC via influencing cell growth and apoptosis. Thus, TRAF6 might become a predictive and therapeutic biomarker for HCC.

20.
Onco Targets Ther ; 9: 5061-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27574447

RESUMO

BACKGROUND: It has been reported that deregulation or dysfunction of microRNAs (miRNAs) plays an essential part in the hepatocarcinogenesis. However, the contribution and mechanism of microRNA-30a-5p (miR-30a-5p) in hepatocellular carcinoma (HCC) remains largely unknown. Therefore, our aim was to investigate the clinicopathological role of miR-30a-5p in HCC tissues and explore its potential pathways in this study. METHODS: The expression of miR-30a-5p was measured in 95 HCC and adjacent noncancer tissues by real-time reverse transcription quantitative polymerase chain reaction. The relationship between miR-30a-5p expression levels and clinicopathological parameters was also analyzed. Furthermore, the potential target genes of miR-30a-5p were collected via online prediction and literature searching. Gene ontology and pathway enrichment analyses were used to identify the possible function of miR-30a-5p in HCC. RESULTS: Compared with adjacent noncancer tissues (2.23±0.77), expression level of miR-30a-5p was significantly lower in HCC tissues (1.26±0.66, P<0.001). MiR-30a-5p expression was evidently correlated with tumor nodes, metastasis, tumor-node-metastasis stage, portal vein tumor embolus, vascular invasion, and status of tumor capsule (all P<0.05). A total of 878 genes were finally used for the biological informatics analyses. These prospective target genes were highly enriched in various key pathways, for instance, Ubiquitin-mediated proteolysis, Axon guidance, Neurotrophin signaling pathway, Amyotrophic lateral sclerosis, and ErbB signaling pathway. CONCLUSION: In conclusion, this study clarifies that the downregulation of miRNA-30a-5p might play a vital part in the incidence and progression of HCC via targeting various prospective genes and pathways. Future validation is required to further explore the prospective molecular mechanism of miR-30a-5p in HCC.

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