Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Aging (Albany NY) ; 15(18): 9695-9717, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37728407

RESUMO

Cuproptosis is a novel type of copper-induced cell death and is considered as a new therapeutic target for many cancers. Distant metastases occur in about 40% of patients with advanced renal cell carcinoma (RCC), with a poor 5-year prognosis of about 10%. Through a series of comprehensive analyses, four differentially expressed cuproptosis-related lncRNAs (DECRLs) were identified as candidate biomarkers for RCC. The risk model constructed by using these four DECRLs can better predict the prognosis of patients with RCC, which is determined by the receiver operating characteristic (Time dependent area under curve value at 1-year, 3-year, 5-year, and 10-year were 0.82, 0.80, 0.76, and 0.73 respectively). There were significant differences in immune status between high-risk and low-risk RCC patients. The differentially expressed gene enrichment terms between high- and low-risk patients was also dominated by immune-related terms. The risk score was also correlated with immunotherapy as measured by the tumor immune dysfunction and exclusion (TIDE) score. In addition, we also found that the sensitivity of many chemotherapy drugs varies widely between high- and low-risk patients. The sensitivity of the three chemotherapy drugs (AZD4547, Vincristine, and WEHI-539) varied among high- and low-risk patients, and was significantly negatively correlated with risk values, suggesting that they could be used as clinical treatment drugs for RCC. Our study not only obtained four potential biomarkers, but also provided guidance for immunotherapy and chemotherapy treatment of RCC, as well as new research strategies for the screening of other cancer biomarkers and sensitive drugs.

2.
Biomed Res Int ; 2022: 2390764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303582

RESUMO

Breast cancer (BC) is one of the most common malignancies affecting women. Ferroptosis is a novel cancer treatment option. The present study is aimed to identify suitable ferroptosis-related lncRNAs to predict and diagnose BC. Differential expression and Cox regression analyses were used to screen suitable prognostic biomarkers and construct a suitable risk model. We identified four ferroptosis-related differentially expressed lncRNAs (FR-DELs) (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3), which were independently correlated with the overall survival of BC patients. The area under the curve value of the prognostic model using those four biomarkers was over 0.60 in all three groups. The sensitivity and specificity of the diagnostic model using those four biomarkers were 86.89% and 86.73%, respectively. Our present study indicated that these four FR-DELs (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3) could be prognostic biomarkers for BC, although clinical validation studies are required.


Assuntos
Neoplasias da Mama , Ferroptose , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Estimativa de Kaplan-Meier , Prognóstico
3.
Front Genet ; 12: 750997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925447

RESUMO

Almost 75% of renal cancers are renal clear cell carcinomas (KIRC). Accumulative evidence indicates that epigenetic dysregulations are closely related to the development of KIRC. Cancer immunotherapy is an effective treatment for cancers. The aim of this study was to identify immune-related differentially expressed genes (IR-DEGs) associated with aberrant methylations and construct a risk assessment model using these IR-DEGs to predict the prognosis of KIRC. Two IR-DEGs (SLC11A1 and TNFSF14) were identified by differential expression, correlation analysis, and Cox regression analysis, and risk assessment models were established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.6907. In addition, we found that risk scores were significantly associated with 31 immune cells and factors. Our present study not only shows that two IR-DEGs can be used as prognosis signatures for KIRC, but also provides a strategy for the screening of suitable prognosis signatures associated with aberrant methylation in other cancers.

4.
Cancer Cell Int ; 21(1): 591, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736453

RESUMO

BACKGROUND: Ferroptosis is a recently recognised new type of cell death which may be a potential target for cancer therapy. In the present study, we aimed to screen ferroptosis-related differentially expressed long non-coding RNAs as biomarkers to predict the outcome of kidney renal clear cell carcinoma. METHODS: RNAseq count data and corresponding clinical information were obtained from the Cancer Genome Atlas database. Lists of ferroptosis-related genes and long non-coding RNAs were obtained from the FerrDb and GENCODE databases, respectively. The candidate prognostic signatures were screened by Cox regression analyses and least absolute shrinkage and selection operator analyses. RESULTS: Three ferroptosis-related long non-coding RNAs (DUXAP8, LINC02609, and LUCAT1) were significantly correlated with the overall survival of kidney renal clear cell carcinoma independently. Kidney renal clear cell carcinoma patients with high-risk values displayed worse OS. Meanwhile, the expression of these three ferroptosis-related long non-coding RNAs and their risk scores were significantly correlated with clinicopathological features. Principal component analyses showed that patients with kidney renal clear cell carcinoma have differential risk values were well distinguished by the three ferroptosis-related long non-coding RNAs. CONCLUSIONS: The present study suggests that the risk assessment model constructed by these three ferroptosis-related long non-coding RNAs could accurately predict the outcome of kidney renal clear cell carcinoma. We also provide a novel perspective for cancer prognosis screening.

5.
Front Oncol ; 11: 661846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485113

RESUMO

Colorectal cancer (CRC) is one of the most common cancers. Almost 1/3 of CRC are rectal cancer, and 95% of rectal cancers are rectal adenocarcinoma (READ). Increasing evidences indicated that long noncoding RNAs (lncRNAs) have important role in the genesis and development of cancers. The purpose of our present study was to identify the differential expression lncRNAs which potentially related with immune cells infiltration and establish a risk assessment model to predict the clinical outcome for READ patients. We obtained three immune-related differential expression lncRNAs (IR-DELs) (C17orf77, GATA2-AS1, and TPT1-AS1) by differential expression analysis following correlation analysis and Cox regression analysis. A risk assessment model were constructed by integrating these analysis results. We then plotted the 1-, 3-, and 5-year ROC curves depending on our risk assessment model, which suggested that all AUC values were over 0.7. In addition, we found that the risk assessment model was correlated with several immune cells and factors. This study suggested that those three signatures (C17orf77, GATA2-AS1, and TPT1-AS1) screened by pairing IR-DELs could be prognosis markers for READ patients and might benefit them from antitumor immunotherapy.

6.
Front Genet ; 12: 690053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306030

RESUMO

Colorectal cancer (CRC) is one of the most common cancers. Almost 80% of CRC cases are colon adenocarcinomas (COADs). Several studies have indicated the role of immunotherapy in the treatment of various cancers. Our study aimed to identify immune-related long non-coding RNAs (lncRNAs) and to use them to construct a risk assessment model for evaluating COAD prognosis. Using differential expression, correlation, and Cox regression analyses, we identified three immune-related differentially expressed lncRNAs (IR-DELs) and used them to construct a risk assessment model. The area under the curve (AUC) for each receiver operating characteristic (ROC) curve at 3-, 5-, and 10-years were greater than 0.6. In addition, the risk assessment model was correlated with several immune cells and factors. The three IR-DELs (AC124067.4, LINC02604, and MIR4435-2HG) identified in this study can be used to predict outcomes for patients with COAD and might help in identifying those who can benefit from anti-tumor immunotherapy.

7.
BMC Med Genomics ; 14(1): 116, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910576

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. METHODS: In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. RESULTS: Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. CONCLUSION: This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Metilação de DNA
8.
BMC Med Genomics ; 14(1): 72, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750388

RESUMO

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC. METHODS: All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. RESULTS: We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year. CONCLUSION: The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.


Assuntos
Carcinoma de Células Renais , Redes Reguladoras de Genes , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs , Prognóstico , RNA Mensageiro/genética
9.
Ther Apher Dial ; 25(6): 926-930, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33675574

RESUMO

Microwave ablation has been increasingly used to secondary hyperparathyroidism (SHPT) in patients with maintenance hemodialysis. However, the current data are inconclusive. This study was to assess the long-term outcomes of microwave ablation on SHPT. We enrolled 53 SHPT patients who underwent microwave ablation. Primary outcome measures were the rate of achieving recommended goal for iPTH and the events of all-cause death during the follow-up period. Survival analysis was performed to assess the long-term prognosis. During follow-up period of 42.4 ± 15.6 months (range, 12-70 months), there were 12 all-cause deaths, and the cumulative proportion surviving was 0.74. The rates of achieving the recommended goal for iPTH were 62.3% at 1 month, 57.7% at 6 months, 51.0% at 12 months, 62.5% at 24 months, and 68.8% at 36 months, respectively. Microwave ablation produces a lasting resolution of secondary hyperparathyroidism in about 60% of patients with maintenance hemodialysis. The characteristics of patients suitable for microwave ablation should be clarified in the future.


Assuntos
Técnicas de Ablação/métodos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/métodos , Feminino , Seguimentos , Humanos , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
Front Oncol ; 11: 774558, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35087751

RESUMO

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most common malignancies of the female genital tract. Ferroptosis and immunity regulate each other and play important roles in the progression of CESC. The present study aimed to screen ferroptosis- and immune-related differentially expressed genes (FI-DEGs) to identify suitable prognostic signatures for patients with CESC. We downloaded the RNAseq count data and corresponding clinical information of CESC patients from The Cancer Genome Atlas database; obtained recognized ferroptosis- and immune-related genes from the FerrDb and ImmPort databases, respectively; and screened for suitable prognostic signatures using a series of bioinformatics analyses. We identified eight FI-DEGs (CALCRL, CHIT1, DES, DUOX1, FLT1, HELLS, SCD, and SDC1) that were independently correlated with the overall survival of patients with CESC. The prediction model constructed using these eight FI-DEGs was also independently correlated with overall survival. Both the sensitivity and specificity of the prediction model constructed using these eight signatures were over 60%. The comprehensive index of ferroptosis and immune status was significantly correlated with the immunity of patients with CESC. In conclusion, the risk assessment model constructed with these eight FI-DEGs predicted the CESC outcomes. Therefore, these eight FI-DEGs could serve as prognostic signatures for CESC.

11.
Front Mol Biosci ; 8: 763697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35118117

RESUMO

Background: Ferroptosis is a novel regulated cell death that is characterized by iron-dependent oxidative damage. Renal cancer is the second most common cancer of the urinary system, which is highly correlated with iron metabolism. The aim of our present study was to identify suitable ferroptosis-related prognosis signatures for renal cancer. Methods: We downloaded the RNA-seq count data of renal cancer from The Cancer Genome Atlas database and used the DESeq2, Survival, and Cox regression analyses to screen the prognosis signatures. Results: We identified 5 ferroptosis-related differentially expressed lncRNAs (FR-DELs) (DOCK8-AS1, SNHG17, RUSC1-AS1, LINC02609, and LUCAT1) to be independently correlated with the overall survival (OS) of patients with renal cancer. The risk assessment model and diagnosis model constructed by those 5 FR-DELs could well predict the outcome and the diagnosis of renal cancer. Conclusion: Our present study not only suggested those 5 FR-DELs could be used as prognosis and diagnosis signatures for renal cancer but also provided strategies for other cancers in the screening of ferroptosis-related biomarkers.

12.
Eur J Pharmacol ; 891: 173704, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33137333

RESUMO

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily which is correlated with pain related hypersensitivity. Recent results indicated that the hyperactive phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway may be a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2. Resveratrol is one of the most widely studied polyphenols with several beneficial properties. In the present study, we investigated the effects of resveratrol on the pain related hypersensitivity. And we found that the up-regulated phosphorylation of S6 could be suppressed by resveratrol. The nocifensive behavior duration time to heat and chemical algogens stimulation in Cntnap2-deficiency (Cntnap2-/-) mice could be attenuated by resveratrol. Our results indicated that resveratrol could rescue the pain related hypersensitivity for Cntnap2-/- mice may be via mTOR signaling pathway.


Assuntos
Analgésicos/farmacologia , Hiperalgesia/tratamento farmacológico , Proteínas de Membrana/deficiência , Proteínas do Tecido Nervoso/deficiência , Limiar da Dor/efeitos dos fármacos , Resveratrol/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hiperalgesia/genética , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Fosforilação , Proteína S6 Ribossômica/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo
13.
Biomed Res Int ; 2020: 7905380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964043

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors. METHODS: In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers. RESULTS: We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly. CONCLUSION: In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Prognóstico , RNA Mensageiro/genética , Análise de Sobrevida , Taxa de Sobrevida
14.
Hemodial Int ; 23(2): 247-253, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30815995

RESUMO

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a serious and common problem in patients undergoing maintenance hemodialysis. Minimally invasive microwave ablation (MWA) has been used to treat SHPT and shows some advantages. However, its efficacy is still undefined. The primary purpose of this study was to determine the efficacy and safety of MWA compared to total parathyroidectomy plus forearm autotransplantation. METHODS: The SHPT patients who were undergoing maintenance hemodialysis (follow-up for 6 to 24 months after treatments) were divided into a MWA group (n = 33) and a parathyroidectomy group (n = 48). The efficacy (serum intact parathyroid hormone [iPTH], calcium, and phosphorus levels) and safety (hoarseness, hypocalcaemia, and persistently low iPTH) were compared between the two groups. Additionally, the study explored potential predictors of response to MWA by a logistic regression analysis. FINDINGS: There were no significant differences in baseline characteristics between the two groups. The rates of achieving the recommended goal for iPTH were significantly higher in the MWA group than that in the parathyroidectomy group at all follow-up times: 57.58% vs. 12.50% at one-day (P < 0.001), 45.45% vs. 16.67% at 1-week (P = 0.005), 57.58% vs. 16.67% at 2-week (P < 0.001), 57.58% vs. 22.92% at 1-month (P = 0.002), and 69.70% vs. 35.42% at 3-month (P = 0.002), 76.47% vs. 28.57% at 6-month (P = 0.005), 87.50% vs. 47.37% at 12-month (P = 0.008), and 81.82% vs. 52.63% at 24-month (P = 0.015), respectively. However, there were no significant differences for phosphorus or calcium at any of the follow-up times (P > 0.05). The persistently low iPTH was more in the parathyroidectomy group (64.6%) than that in the MWA group (0%) (P < 0.001), but there was no significant difference in hoarseness or hypocalcaemia (P > 0.05). Baseline levels of iPTH (P = 0.021) and patient age (P = 0.011) were determined as predictors by univariate logistic regression analysis. CONCLUSION: The MWA could be an alternative to parathyroidectomy for SHPT but its eventual superiority has to be demonstrated by a proper study.


Assuntos
Técnicas de Ablação/métodos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/terapia , Paratireoidectomia/métodos , Diálise Renal/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos , Adulto Jovem
15.
Cancer Biomark ; 19(1): 27-34, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28269749

RESUMO

BACKGROUND: Aurora A kinase is frequently overexpressed in a variety of tumor types, including the prostate. However, the function of Aurora A in autophagy in prostate cancer has not been investigated. Here, we aimed to study the functioning mechanism and autophagy associated signaling pathways of Aurora A in prostate cancer. METHODS: To investigate the biological function of Aurora A, down-regulation of Aurora A was performed followed by functional testing assays. Immunohistochemistry was used to detect the expression of Aurora A in human prostate cancer specimens. CCK8, Transwell, flow cytometric analysis and measurement of tumor formation in nude mice were performed to test the effects of Aurora A down-regulation in vivo and in vitro. Signaling pathway analysis was performed by using Western blot. Autophagy activity was measured by monitoring the expression levels of LC3-II. RESULTS: Aurora A overexpression was significantly higher in human prostate cancer specimens than in BPH. Furthermore, Aurora A knockdown inhibited the proliferation of prostate cancer cells by suppressing the Akt pathway, indicating that Akt is a novel Aurora A substrate in prostate cancer. Additionally, Aurora A down-regulation prompts autophagy in prostate cancer cells. Most importantly, Aurora A ablation almost fully abrogates tumorigenesis in nude mice, suggesting that Aurora A is a key oncogenic effector in prostate cancer. CONCLUSIONS: Taken together, our data suggest that Aurora-A plays an important role in the suppression of autophagy by inhibiting the phosphorylation of Akt, which in turn prevents autophagy-induced apoptosis in prostate cancer.


Assuntos
Aurora Quinase A/genética , Autofagia/genética , Proliferação de Células/genética , Neoplasias da Próstata/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Proteína Oncogênica v-akt/genética , Fosforilação , Neoplasias da Próstata/patologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
16.
BJU Int ; 118(4): 578-89, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26775686

RESUMO

OBJECTIVE: To explore the relation between microRNA-30a (miR-30a) and Notch1, and to evaluate the potential prognostic role of miR-30a in invasive urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: In all, 50 invasive UCB tissue specimens, along with the adjacent bladder tissue specimens were obtained, and the clinical parameters of the 50 patients were analysed. Bioinformatics analysis was performed and miR-30a was selected as a potential miRNA targeting Notch1, with a luciferase assay performed to verify the binding site between miR-30a and Notch1. Quantitative real-time reverse transcriptase-polymerase chain reaction was used to assess the RNA expressions of miR-30a and Notch1, while Western Blotting and immunohistochemical staining were used to assess the protein expression of Notch1. Finally, cell proliferation, cell cycle, cell migration and invasion assays were used to evaluate the cellular effects of miR-30a and Notch1 on the UCB cell lines T24 and 5637. RESULTS: MiR-30a was downregulated in tumour tissues when compared with adjacent bladder tissues (P < 0.001), negatively correlating with Notch1 messenger RNA (R(2) 0.106, P = 0.021) in invasive UCB, and miR-30a expression further decreased in patients with shorter overall survival and disease-free survival (P = 0.039 and P = 0.037, respectively). The luciferase assay showed that miR-30a inhibited the Notch1 3'-untranslated region reporter activities in the T24 and 5637 cell lines (both P < 0.001). Both miR-30a and small interfering RNA Notch1 negatively regulated cell proliferation (P = 0.002 and P = 0.035 in T24; P = 0.029 and P = 0.037 in 5637 cell lines), activated cell cycle arrest (both P < 0.001 in T24; both P < 0.001 in 5637 cell lines), and prevented cellular migration (both P < 0.001 in T24; P = 0.003 and P < 0.001 in 5637 cell lines) and invasion (P = 0.009 and P = 0.006 in T24; P = 0.006 and P = 0.002 in 5637 cell lines) abilities. Ectopic Notch1 without the 3'untranslated region partially rescued the above-mentioned cellular effects of over-expressed miR-30a on T24 and 5637 cells. CONCLUSIONS: MiR-30a lessens cellular malignancy by antagonising oncogene Notch1 and plays an effective prognostic role in invasive UCB.


Assuntos
Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , MicroRNAs/fisiologia , Receptor Notch1/antagonistas & inibidores , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade
17.
Tumour Biol ; 37(4): 5165-70, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26547586

RESUMO

There is increasing evidence suggesting that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) was involved in tumorigenesis. However, its role in bladder cancer remains unclear. In this study, we aimed to study the clinical correlation and biological significance of ESCO1 in bladder cancer. Our results showed that ESCO1 was significantly over-expressed in bladder cancer tissues compared with that in adjacent normal tissues. And, increased ESCO1 expression was significantly associated with higher grade (P < 0.001), higher tumor stage (P = 0.014), and multifocality (P = 0.042). Kaplan-Meier analysis and Cox proportional hazards model were performed to determine the prognostic significance of ESCO1, and the results showed that ESCO1 is a useful prognostic marker for bladder cancer patients. Moreover, we found that ESCO1 knockdown inhibited the growth, migration, and invasion of bladder cancer cells. In conclusion, our findings indicated that ESCO1 may play an important role in human bladder cancer, and ESCO1 might serve as a novel target and prognosis factor for human bladder cancer.


Assuntos
Acetiltransferases/biossíntese , Biomarcadores Tumorais/biossíntese , Recidiva Local de Neoplasia/genética , Prognóstico , Neoplasias da Bexiga Urinária/genética , Acetiltransferases/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia
18.
Drug Des Devel Ther ; 9: 5911-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26604689

RESUMO

BACKGROUND: PACE4 is a proprotein convertase capable of processing numerous substrates involved in tumor growth, invasion, and metastasis. However, the precise role of PACE4 during prostate cancer cell apoptosis has not been reported. METHODS: In the present study, human prostate cancer cell lines DU145, LNCaP, and PC3 were transfected with PACE4 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. RESULTS: We revealed that PACE4 siRNA exhibited antitumor activity by inducing apoptosis, as determined by Cell Counting Kit-8 (CCK-8), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide (MTT) assay, cell cycle analysis, Hoechst staining, caspase-3/7 activity, and western blot analysis. In addition, PACE4 siRNA significantly increased the ratio of Bax/Bcl-2, which led to the release of cytochrome c. Moreover, PACE4 siRNA also induced endoplasmic reticulum stress by increasing the expression of GRP78, GRP94, p-PERK, and p-eIF2α. The ratio of Bax/Bcl-2 and GRP78 were also increased in PACE4 gene knockdown prostate cancer cells compared with the control cells. CONCLUSION: These data demonstrate that PACE4 siRNA may exert its antitumor activity through mitochondrial and endoplasmic reticulum stress signaling pathways, indicating it may be a novel therapeutic target for prostate cancer.


Assuntos
Apoptose/genética , Estresse do Retículo Endoplasmático/genética , Pró-Proteína Convertases/genética , Neoplasias da Próstata/patologia , Serina Endopeptidases/genética , Linhagem Celular Tumoral , Citocromos c/metabolismo , Chaperona BiP do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Mitocôndrias/metabolismo , Neoplasias da Próstata/genética , RNA Interferente Pequeno/administração & dosagem , Transdução de Sinais/genética
19.
Tumour Biol ; 36(8): 6133-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25773392

RESUMO

SOX genes play an important role in a number of developmental processes. The transcription factor SOX11 is one of the members of the SOX family emerging as important transcriptional regulators. The aim of this study was to investigate the role of SOX11 in prostate cancer (PCa) and its expression pattern and clinical significance. The gene expression of SOX11 in human PCa tissues compared with benign prostate hyperplasia (BPH) tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. SOX11 overexpression cell model was used to examine the role of SOX11 in cell growth and metastasis in vitro. The results showed that the positive rate of SOX11 staining was 16.67 % (10/60) in cases of prostatic carcinoma and 81.67 % (49/60) in cases of BPH, and the difference of SOX11 expression between PCa and BPH was statistically significant (P < 0.001). SOX11 mRNA level was lowly expressed in PCa cell lines compared to RWPE-1. SOX11 overexpression suppresses PCa cell migration and invasion. In conclusion, our findings demonstrate that SOX11 could suppress cell proliferation, migration, and invasion of PCa in vitro.


Assuntos
Proliferação de Células/genética , Neoplasias da Próstata/genética , Fatores de Transcrição SOXC/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/biossíntese , Fatores de Transcrição SOXC/genética
20.
Int J Clin Exp Med ; 8(10): 19418-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770585

RESUMO

PURPOSE: To evaluate clinical efficacy and safety of two micron laser vaporesection combined with transurethral resection of the prostate (TURP) in treating benign prostatic hyperplasia (BPH). METHODS: In total, 340 BPH patients aged 62-86 years, were treated with two micron laser vaporesection plus TURP. Mean prostatic volume was measured as 38-182 ml. Operative time, intraoperative hemorrhage volume, time of postoperative bladder irrigation, time of indwelling urinary catheter and surgical complications were examined. International Prostate Symptom Score (IPSS), quality of life score (QOL), maximal urinary flow rate (Qmax) and post void residual urine volume (PVR) were analyzed. RESULTS: All cases underwent the surgery successfully. No transurethral resection syndrome was noted. Mean operative time was (72±15) min. Mean intra operative hemorrhage volume was (48.4±13.0) ml. Four patients were transfused with 2 U of suspended red blood cells. Time of postoperative bladder irrigation ranged from 0.5-2.5 d. Time of indwelling urinary catheter was 3-6 d. After removing urinary catheter, mild urinary irritation symptoms were noted in 19 cases. Ten patients developing urinary infection were recovered following anti-infection therapy. One with secondary urethral stenosis was healed after urethral dilatation for three times. Postoperative IPSS, QOL, Qmax and PVR were (6.0±2.0), (2.0±0.2), (18.5±1.6) ml/s and (11.0±4.0) ml, significantly improved compared with preoperative levels (all P<0.05). Fifty eight cases with normal sexual function retained sexual function postoperatively and had no retrograde ejaculation. CONCLUSIONS: Two micron laser vaporesection plus TURP is efficacious and safe in treating BPH with mild lower urinary tract symptoms and perioperative complications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...