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1.
Clin Transl Med ; 12(4): e691, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35474446

RESUMO

BACKGROUND: Gastric carcinoma (GC) is one of the most deadly diseases due to tumour metastasis and resistance to therapy. Understanding the molecular mechanism of tumour progression and drug resistance will improve therapeutic efficacy and develop novel intervention strategies. METHODS: Differentially expressed long non-coding RNAs (lncRNAs) in clinical specimens were identified by LncRNA microarrays and validated in different clinical cohorts by quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridisation and bioinformatics analysis. Biological functions of lncRNA were investigated by using cell proliferation assays, migration assays, xenograft tumour models and bioinformatics analysis. Effects of lncSLCO1C1 on GC cell survival were assessed by comet assays and immunofluorescence assays. Underlying molecular mechanisms were further explored by using a number of technologies including RNA pull-down, mass spectrometry analysis, RNA immunoprecipitation, co-immunoprecipitation, miRNA sequencing, luciferase reporter assays and molecular modelling. RESULTS: LncSLCO1C1 was highly upregulated in GC tissue samples and associated with GC patients' poor overall survival. Overexpression of lncSLCO1C1 promoted proliferation and migration, whereas decreased lncSLCO1C1 expression produced the opposite effects. lncSLCO1C1 also mediated tumour resistance to chemotherapy with oxaliplatin by reducing DNA damage and increasing cell proliferation. Despite sequence overlapping between lncSLCO1C1 and PDE3A, alternations of PDE3A expression had no effect on the GC cell progression, indicating that lncSLCO1C1, not PDE3A, related with the progression of GC cells. Mechanistically, lncSLCO1C1 serves as a scaffold for the structure-specific recognition protein 1 (SSRP1)/H2A/H2B complex and regulates the function of SSRP1 in reducing DNA damage. Meanwhile, lncSLCO1C1 functions as a sponge to adsorb miR-204-5p and miR-211-5p that target SSRP1 mRNA, and thus increases SSRP1 expression. Patients with high expressions of both lncSLCO1C1 and SSRP1 have poor overall survival, highlighting the role of lncSLCO1C1 in GC progression. CONCLUSIONS: LncSLCO1C1 promotes GC progression by enhancing cell growth and preventing DNA damage via interacting and scaffolding the SSRP1/H2A/H2b complex and absorbing both miR-211-5p and miR-204-5p to increase SSRP1 expression.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transportadores de Ânions Orgânicos , Oxaliplatina/farmacologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismo
2.
Nanomedicine (Lond) ; 16(25): 2255-2267, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569291

RESUMO

Aim: Long noncoding RNA (lncRNA) BC032469-dependent gold nanoparticle molecular beacons (AuNP-MB) were constructed for the detection of gastric cancer cells. Materials & methods: The AuNP-MBs were prepared according to well-established procedures based on the Au-S interaction between the gold lattice and thiol functionalized oligonucleotides. More importantly, the stability and targeting ability of AuNP-MB were verified by a series of in vitro and in vivo experiments. Results: The lncRNA-dependent probes were successfully utilized for AuNP-MB-based intracellular imaging, with fluorescence effectively emitted in GC cells, but not in normal cells. Notably, such fluorescent emission was positively correlated with lncRNA BC032469 expression. Conclusion: The authors developed an effective fluorescent imaging probe for the recognition of gastric cancer cells.


Assuntos
Nanopartículas Metálicas , RNA Longo não Codificante , Neoplasias Gástricas , Corantes Fluorescentes , Ouro , Humanos , RNA Longo não Codificante/genética , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genética
3.
Drug Des Devel Ther ; 13: 3171-3180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564833

RESUMO

BACKGROUND: Emodin, a major component of Polygonum multiflorum (PM), has been reported to exert both protective and toxic effects in several cell types. However, the effects and underlying mechanisms of action of emodin in hepatic cells are still obscure. METHODS: The present study used the normal human liver cell line L02 to investigate the effects and mechanisms of emodin in hepatic cells. After treatment with emodin, L02 cells were examined for viability, apoptosis and autophagy with the Cell Counting Kit-8 (CCK-8), annexin V/PerCP staining and GFP-LC3 plasmid transfection. The expression of proteins including cleaved caspase-3, LC3B-I/II, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and actin was examined by using Western blot. RESULTS: Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone. CONCLUSION:  In conclusion, emodin exhibited cytotoxicity in the L02 human hepatic cell line by promoting apoptosis, and it also induced autophagy through the suppression of the PI3K/AKT/mTOR signalling pathway. The autophagy could play a protective role following emodin treatment.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Emodina/farmacologia , Hepatócitos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Emodina/química , Fallopia multiflora/química , Hepatócitos/metabolismo , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo
4.
Chin Med J (Engl) ; 130(22): 2661-2665, 2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29133752

RESUMO

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.


Assuntos
Morcelação/efeitos adversos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Adulto , China , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos
5.
Oncol Lett ; 14(2): 2523-2530, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781691

RESUMO

Although numerous long non-coding RNAs (lncRNAs) have been identified to be important in human cancer, their potential regulatory roles in epithelial tumorigenesis and tumor progression in ovarian cancer remain unclear. The purpose of the present study was to investigate lncRNAs that were differentially expressed (DE) in epithelial ovarian cancer and to explore their potential functions. The lncRNA profiles in five pairs of human epithelial ovarian cancer tissues and their adjacent normal tissues were described using microarrays. The results of the microarray analysis revealed that 672 upregulated and 549 downregulated (fold-change ≥2.0) lncRNAs were DE between the cancerous and normal tissues. Reverse transcription-quantitative polymerase chain reaction was used to validate the microarray results using four upregulated (RP11-1C1.7, XLOC_003286, growth arrest-specific 5 and ZNF295-AS1) and four downregulated (protein tyrosine kinase 7, maternally expressed gene 3, AC079776.2 and ribosomal protein lateral stalk subunit P0 pseudogene 2) lncRNAs. Furthermore, gene ontology and pathway analyses were used to carry out functional analyses of the candidate genes of DE lncRNAs. The results identified lncRNAs with significantly altered expression profiles in human epithelial ovarian cancer cells compared with those in adjacent normal cells. These data offer new insights into the occurrence and development of epithelial ovarian cancer, and these lncRNAs may provide novel molecular biomarkers for further research on epithelial ovarian cancer.

6.
Int J Nanomedicine ; 12: 1815-1825, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331307

RESUMO

Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.


Assuntos
Nanoestruturas/uso terapêutico , Nanotecnologia/tendências , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Nanoestruturas/ultraestrutura
7.
Int J Nanomedicine ; 11: 3023-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27486320

RESUMO

Gastric cancer is one of the leading causes of tumor-related deaths in the world. Current treatment options do not satisfy doctors and patients, and new therapies are therefore needed. Cerium oxide nanoparticles (CNPs) have been studied as a potential therapeutic approach for treating many diseases. However, their effects on human gastric cancer are currently unknown. Therefore, in this study, we aimed to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and BGC823). Gastric cancer cells were cocultured with different concentrations of CNPs, and proliferation and migration were measured both in vitro and in vivo. We found that CNPs inhibited the migration of gastric cancer cells when applied at different concentrations, but only a relatively high concentration (10 µg/mL) of CNPs suppressed proliferation. Furthermore, we found that CNPs increased the expression of DHX15 and its downstream signaling pathways. We therefore provide evidence showing that CNPs may be a promising approach to suppress malignant activity of gastric cancer by increasing the expression of DHX15.


Assuntos
Cério/química , Nanopartículas/química , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Metástase Neoplásica , RNA Helicases/genética , RNA Helicases/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/ultraestrutura
8.
Oncotarget ; 7(27): 42474-42484, 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27283901

RESUMO

The early diagnosis and treatment of tumors is of vital significance to increase patient survival. Therefore, we constructed a lentiviral vector expressing tyrosinase (TYR) driven by an optimized human telomerase reverse transcriptase (hTERT) promoter or a cytomegalovirus(CMV) promoter in the hopes of performing noninvasive and real-time tumor-specific imaging. First, hTERT-TYR and CMV-TYR were constructed to infect cancer cell lines (telomerase-negative cell line: U2OS; telomerase-positive cell lines: SGC-7901, SW480 and HepG2). Subsequently, stable tyrosinase-expressing cell lines were sorted by flow cytometry out of these infected cancer cell lines. Then, the mRNA and protein levels of tyrosinase were analyzed. Thetyrosinase activity, melanin production and ferric ion adsorption were measured followed by an MR scan. Consequently the results showed that tyrosinase was only expressed in telomerase-positive tumor cells infected by hTERT-TYR, whereas tyrosinase was expressed in both telomerase-negative and telomerase-positive tumor cells infected by CMV-TYR. Finally, we performed in vivo tumor MR using a clinical 3T MR scanner and found increased signals at T1W1 from telomerase-positive cells infected by hTERT-TYR, which revealed that MR scanning could distinguish cells with hTERT -positive cells from hTERT-negative cells infected with the optimized lentivirus. The mechanism underlying this effect is that tyrosinase promotes melanin production and ferric ion adsorption only in hTERT-expressing cells. Taken together, these data show that this optimized hTERT promoter-driving tyrosinase expression system might be a useful diagnostic tool for the detection of tumors using MR imaging.


Assuntos
Regulação Neoplásica da Expressão Gênica , Espectroscopia de Ressonância Magnética , Monofenol Mono-Oxigenase/metabolismo , Neoplasias/diagnóstico por imagem , Telomerase/genética , Animais , Linhagem Celular Tumoral , Citomegalovirus/genética , Genes Reporter , Terapia Genética/métodos , Células Hep G2 , Humanos , Lentivirus/genética , Melaninas/metabolismo , Camundongos , Camundongos SCID , Transplante de Neoplasias , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo
9.
Stem Cells Int ; 2015: 960387, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26300925

RESUMO

MSCs have become a popular target for developing end-stage liver therapies. In this study, two models of bone marrow chimeric mice were used to construct the liver failure models. Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity. However, the percentage of transdifferentiation was significantly higher than fusion. So it was considered that MSCs which transdifferentiated into hepatocyte-likes cells played important roles for repairing the injuring liver function.

10.
Cancer Lett ; 361(1): 57-66, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-25727320

RESUMO

Heparanase (HPA) is an endoglucuronidase that can promote the shedding of associated cytokines in several types of tumors. However, little is known about what controls the expression of HPA or its role in gastric cancer. In this study, we report for the first time that HGF regulates HPA expression to promote gastric cancer metastasis. In this study, HGF and HPA were found to be significantly expressed in 58 gastric cancer patients. High expression of both HGF and HPA was positively associated with TNM stage, invasion depth and poor prognosis. In MKN74 cells, exogenous HGF significantly increased HPA expression at both the mRNA and protein levels. Further study revealed that HGF first activated PI3K/Akt signaling. NF-κB signaling was activated downstream of PI3K/Akt and promoted HPA expression. However, when c-met, PI3K/Akt or NF-κB signal inhibitors were used, HPA expression was significantly decreased. All of these results indicate that HGF regulates HPA expression by PI3K/Akt and downstream NF-κB signaling. Using bioinformatics and the ChIP assay, p65 was observed to bind to the HPA promoter. Furthermore, HGF significantly induced tumor cell migration, whereas treatment with an NF-κB inhibitor decreased migration. Moreover, when HPA was overexpressed in MKN74 cells, migration was significantly enhanced, and the HGF concentration was increased. However, when HPA was down-regulated in MKN45 cells, migration and HGF levels decreased. Together, these results demonstrate that HGF/c-met can activate PI3K/Akt and downstream NF-κB signaling to promote HPA expression and subsequent tumor metastasis.


Assuntos
Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucuronidase/genética , Fator de Crescimento de Hepatócito/farmacologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/secundário , Western Blotting , Proliferação de Células/efeitos dos fármacos , Imunoprecipitação da Cromatina , Feminino , Mucosa Gástrica/metabolismo , Glucuronidase/metabolismo , Humanos , Luciferases/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Ativação Transcricional/efeitos dos fármacos , Células Tumorais Cultivadas , Regulação para Cima , Cicatrização/efeitos dos fármacos
11.
Cancer Lett ; 360(2): 151-9, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25662441

RESUMO

In humans, telomerase reverse transcriptase (hTERT) determines the activity of telomerase. hTERT is an ideal anticancer target because it is universally expressed in cancer cells and plays a crucial role in carcinogenesis. In this study, we report the miR-1182-mediated post-transcriptional regulation of hTERT. Over-expression of miR-1182 in different gastric cancer cells decreased hTERT protein levels. Bioinformation and dual-luciferase assays revealed that miR-1182 modulated hTERT by binding to its open reading frame (ORF), and this miRNA recognizes elements in the nucleotide region between 2695 and 2719 of hTERT mRNA. Over-expression of hTERT by transfecting pIRES2-hTERT into U2OS cells was abolished by miR-1182, while pIRES2-hTERT-MT, in which miR-1182 target site was synonymously mutated, failed to respond to miR-1182. Further investigation revealed that miR-1182 inhibited gastric cancer proliferation and migration by targeting the ORF1 of hTERT. We also found that miR-1182 could attenuate the proliferative and metastatic potential of SGC-7901 cell in vivo. Moreover, we found a statistically significant inverse correlation between miR-1182 and hTERT protein levels in tissues from 42 gastric cancer patients. These data indicate that miR-1182 suppresses TERT, and thus it could be an effective target for the treatment of gastric cancer.


Assuntos
MicroRNAs/genética , Fases de Leitura Aberta , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Telomerase/genética , Regiões 3' não Traduzidas , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células HEK293 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/biossíntese , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Sequências Reguladoras de Ácido Ribonucleico , Neoplasias Gástricas/metabolismo , Telomerase/metabolismo
12.
Food Funct ; 5(7): 1520-8, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24836454

RESUMO

Caffeine is present in a number of dietary sources consumed worldwide. Although its pharmacokinetics has been intensively explored, little is known about complexed caffeine (C-CAF) in aqueous extraction of fermented Pu-er tea. The major components of C-CAF are oxidative tea polyphenols (OTP) and caffeine. Furthermore, the C-CAF can be precipitated in low pH solution. After administering the same amount of total caffeine and comparing the peak level of plasma caffeine with the coffee (contains 0.11 ± 0.01% C-CAF) group, the results showed that the caffeine/OTP (contains 66.67 ± 0.02% C-CAF) group and the instant Pu-er tea (contains 23.18 ± 0.02% C-CAF) group were 33.39% and 25.86% lower, respectively. The concentration of the metabolites of caffeine supports the idea that the absorption of the C-CAF was inhibited in mice. Congruent with this result, the amount of caffeine detected in mice excrement showed that more caffeine was eliminated in the caffeine/OTP group and the Pu-er tea group. The locomotor activity tests of mice demonstrated that the stimulating effect of caffeine in caffeine/OTP and Pu-er tea was weaker than in coffee. Our findings demonstrate that caffeine can be combined with OTP and the absorption of C-CAF is inhibited in mice, thus decreasing the irritation effect of caffeine. This may also be developed as a slow release formulation of caffeine.


Assuntos
Cafeína/farmacocinética , Chá/química , Animais , Cafeína/administração & dosagem , Cafeína/sangue , Café/química , Feminino , Fermentação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polifenóis/administração & dosagem , Polifenóis/sangue , Polifenóis/farmacocinética
13.
Bull Environ Contam Toxicol ; 91(4): 460-4, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23918231

RESUMO

This paper reports in vitro effects of individual heavy metals (Cd(2+), Cu(2+) and Hg(2+)), and PAHs, including benzo[a]pyrene(BaP), indeno[1,2,3-cd]pyrene (IP) and fluoranthene (FL), and their mixtures on ethoxyresorufin-O-deethylase (EROD) activities using a plate-reader method. The results showed that all three metals inhibited EROD activity, while BaP/IP significantly induced the enzyme. However, FL alone decreased EROD activity. Moreover, co-treatment with BaP/IP and heavy metals inhibited PAH-induced EROD activities, while combined exposure to FL and heavy metals induced FL-inhibited EROD activities.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Fígado/enzimologia , Metais Pesados/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Fígado/efeitos dos fármacos , Tilápia/fisiologia
14.
Mol Biol Rep ; 40(2): 1711-20, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23108995

RESUMO

Resistance to anoikis, the subtype of apoptosis induced by lack of matrix adhesion, contributes to malignant transformation and development of metastasis. MicroRNAs play key regulatory roles in tumorigenesis and metastasis. In this study, we described that miR-26a, which is usually downregulated in tumor cells, is involved in the acquisition of anoikis-resistance of human esophageal adenocarcinoma (EA) cells. Results of qRT-PCR in clinical samples showed that downregulated miR-26a expression is related to tumorigenesis and metastasis of EA. In vitro experiments determined that miR-26a directly participates in the regulation of cell cycle and anoikis of human EA OE33 cells. Further, we identified that Rb1 is the direct functional target of miR-26a, and revealed that the reduction of miR-26a expression leads to increased Rb1 protein level and thus inhibits the function of E2F1, by which it influences the phenotypes of cell cycle and anoikis. The findings we reported here presented the evidence that miR-26a may be involved in regulation of anoikis-resistance of EA cells. Targeting miR-26a may provide a novel strategy to inhibit metastasis.


Assuntos
Adenocarcinoma/metabolismo , Anoikis , Fator de Transcrição E2F1/metabolismo , Neoplasias Esofágicas/metabolismo , MicroRNAs/fisiologia , Proteína do Retinoblastoma/genética , Regiões 3' não Traduzidas , Adenocarcinoma/secundário , Animais , Sequência de Bases , Sítios de Ligação , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação para Baixo , Neoplasias Esofágicas/patologia , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , Transplante de Neoplasias , Interferência de RNA , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Transcrição Gênica
15.
Chemphyschem ; 14(1): 198-203, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23203973

RESUMO

2-Ureido-4(1H)-pyrimidinone-bridged ferrocene-fullerene assembly I is designed and synthesized for elaborating the photoinduced electron-transfer processes in self-complementary quadruply hydrogen-bonded modules. Unexpectedly, steady-state and time-resolved spectroscopy reveal an inefficient electron-transfer process from the ferrocene to the singlet or triplet excited state of the fullerene, although the electron-transfer reactions are thermodynamically feasible. Instead, an effective intra-assembly triplet-triplet energy-transfer process is found to be operative in assembly I with a rate constant of 9.2×10(5) s(-1) and an efficiency of 73% in CH(2)Cl(2) at room temperature.

16.
Oncol Lett ; 3(1): 35-38, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22740852

RESUMO

MicroRNAs (miRNAs) are a class of endogenous, small, non-coding RNAs that regulate gene expression by targeting mRNAs and inhibiting expression via translation repression or RNA degradation. Emerging evidence indicates that miRNAs play a crucial role in the pathogenesis of human diseases, including tumor development. We profiled the miRNA expression between mature ovarian teratoma samples and matched normal tissues using miRNA microarrays, followed by validation with quantitative RT-PCR (qRT-PCR). The most highly expressed miRNAs in mature ovarian teratoma tissues were miRNA-520a-5p, miRNA-26b*, miRNA-421, miRNA-492 and miRNA-555, with a 1.3- to 2.6-fold change, whereas the least expressed miRNAs were miRNA-142-3p, let-7a, miRNA-19a, miRNA-34a, miRNA-620, miRNA-934, miRNA-657, miRNA-720, miRNA-22, miRNA-629 and miRNA-214, with a decreased level of 55-87% compared with normal tissues. The findings of the present study are the first to provide an altered miRNA profile for mature ovarian teratomas and differentially expressed miRNAs, which, if validated in future studies, may be essential in the pathogenesis of mature ovarian teratomas.

17.
Zhonghua Jie He He Hu Xi Za Zhi ; 33(7): 500-4, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20979795

RESUMO

OBJECTIVE: To study the relationship between cAMP response element binding protein (CREB) and the interferon-γ (IFN-γ) proximal promoter in patients with tuberculosis. METHODS: CD3(+) T cells were isolated from 25 pulmonary tuberculosis patients, who had been treated in Beijing Chest Hospital from January to December 2007, and 18 PPD-positive healthy donors. After extraction of nuclear proteins, electrophoretic mobility shift assay (EMSA) was performed to determine nuclear protein binding to the IFN-γ proximal promoter in vitro, and the specificity of binding complex was tested by competitive EMSA. Chromatin immunoprecipitation (ChIP) with anti-CREB Ab was used to determine whether CREB binded to the IFN-γ proximal promoter in vivo in live T cells exposed to microbial Ags. Western blotting with anti-CREB Ab was performed to compare the expression level of CREB in tuberculosis patients and PPD-positive healthy donors. Western blotting with Abs specific for serine 133-phosphorylated CREB was performed to determine whether M.tuberculosis Ags elicited phosphorylation of CREB. RESULTS: The results of EMSA showed a low-mobility complex binding to the IFN-γ promoter, and the binding pattern observed was similar for T cells from all 18 PPD-positive healthy donors. However, for T cells from 18 of 25 tuberculosis patients, the low-mobility complex was absent. The results of competitive EMSA showed that these nuclear proteins specifically bound to the IFN-γ promoter region and contained CREB. The results of ChIP showed a 204 bp band yielded in CD3(+) T cells from 10 PPD-positive healthy donors, but 12 tuberculosis patients didn't yield the band. CREB expression markedly decreased in tuberculosis patients compared with healthy donors detected by Western blotting. Furthermore, M. tuberculosis Ags also elicited phosphorylation of CREB in CD3(+) T cells from PPD-positive healthy donors, but not in CD3(+) T cells from tuberculosis patients. CONCLUSIONS: CREB protein binding to IFN-γ proximal promoter was reduced in tuberculosis patients compared with healthy donors. Tuberculosis patients had diminished CREB protein levels, and reduced ability of binding to the IFN-γ promoter.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Interferon gama/genética , Tuberculose Pulmonar/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Linfócitos T/metabolismo , Tuberculose Pulmonar/metabolismo , Adulto Jovem
19.
Brain Res ; 1233: 176-84, 2008 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-18708037

RESUMO

An increasing number of inherited neurodegenerative diseases are known to be caused by the expansion of unstable trinucleotide repeat tracts. Spinocerebellar ataxia type 8 (SCA8) has been identified as being partly caused by a CTG expansion in an untranslated, endogenous antisense RNA that overlaps the Kelch-like 1 (KLHL1) gene. Clinically, SCA8 patients show similar features to those with the other SCAs, including limb and truncal ataxia, ataxic dysarthria and horizontal nystagmus, all of which are signs of dysfunction of the cerebellar system. However, allele sizes within the SCA8 proposed pathogenic range have been reported in patients with ataxia of unknown etiology, in individuals from pedigrees with other SCA or Friedreich's ataxia, and in patients with Alzheimer's disease, schizophrenia or parkinsonism. These observations suggest that mutation of the SCA8 locus might affect neurons other than the cerebellum. Antisense transcripts are known to regulate complementary sense transcripts and are involved in several biologic functions, such as development, adaptive response, and viral infection. In order to test whether SCA8 affects the KLHL1 expression by antisense RNA in brain cells, we examined the expression pattern of KLHL1 and SCA8 in human tissues and in mouse brain regions. SCA8 expression was colocalized with KLHL1 transcript in many brain regions whose functions are correlated to the clinical symptoms of SCA8 patients. These findings lead to the hypothesis of a possible relevance that SCA8 transcript downregulates KLHL1 expression through an antisense mechanism, which then leads to SCA8 neuropathogenesis.


Assuntos
Encéfalo/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ataxias Espinocerebelares/metabolismo , Testículo/metabolismo , Animais , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Hipotálamo/metabolismo , Rim/metabolismo , Masculino , Camundongos , Proteínas dos Microfilamentos/genética , Proteínas do Tecido Nervoso/genética , Pâncreas/metabolismo , Próstata/metabolismo , RNA Longo não Codificante , RNA Mensageiro/análise , RNA não Traduzido , Tálamo/metabolismo , Distribuição Tecidual
20.
Yao Xue Xue Bao ; 43(5): 443-9, 2008 May.
Artigo em Chinês | MEDLINE | ID: mdl-18717328

RESUMO

The current status and latest advances in new technique pseudophase biochromatography are reviewed. After brief introduction to the principle of new technique pseudophase biochromatography, the nature and various influence factors including the compositions, the types of new technique pseudophase biochromatography system are summarized in detail and the aspects of the future applications biochromatography in life science are described.


Assuntos
Biotecnologia/métodos , Cromatografia Capilar Eletrocinética Micelar/métodos , Eletroforese Capilar/métodos , Lipossomos , Animais , Cromatografia Líquida/métodos , Humanos , Bicamadas Lipídicas/química , Retinoides/isolamento & purificação
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