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C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.
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Adipocinas , Inflamação , Animais , Camundongos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Complemento C1q , Inflamação/metabolismoRESUMO
This study aimed to explore the expression profile, prognostic value, regulatory effect, and the underlying mechanism of dysregulation of phosphoglycerate kinase 1 (PGK1) in high-risk human papillomavirus (HPV)-positive cervical epithelial squamous cell carcinoma (CESC). Bioinformatic analysis was performed using the CESC subset of The Cancer Genome Atlas (TCGA)-Cervical Cancer (CESC) and normal cervix in The Genotype-Tissue Expression (GTEx) project. HPV-16 positive CaSki and SiHa cells were used as in vitro cell models. Results showed that compared to the normal cervix, CESC tissues had significantly higher expression of PGK1. CESC patients with the higher 50% expression of PGK1 had substantially shorter disease-specific survival (DSS), and progression-free survival (PFS) compared to the cases with the lower 50% expression of PGK1. PGK1 knockdown impaired, but PGK1 overexpression enhanced the proliferation, colony formation, aerobic glycolytic activities (lactate production, intracellular ATP levels, glucose uptake, and extracellular acidification rate), migration, and invasion of CaSki and SiHa cells. HPV-16 E6/E7 knockdown in CaSki and SiHa cells had limited influence on PGK1 transcription but significantly decreased the half-life of PGK1 protein. E6/E7 knockdown mediated PGK1 downregulation could be blocked by adding MG-132. PGK1 poly-ubiquitination was significantly enhanced after E6/E7 knockdown. In conclusion, this study showed that PGK1 expression might serve as a prognostic biomarker in cervical cancer. Its upregulation contributes to enhanced aerobic glycolysis, migration, and invasion of CESC cells. HPV16 E6/E7 stabilizes PGK1 protein by reducing its poly-ubiquitination.
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Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Oncogênicas Virais , Proteínas E7 de Papillomavirus , Fosfoglicerato Quinase/genética , Estabilidade Proteica , Proteínas Repressoras , Ubiquitinação , Regulação para Cima , Neoplasias do Colo do Útero/genéticaRESUMO
BACKGROUND Ovarian cancer is one of the most common gynecological malignancies and mortality ranks the highest in cancer-associated death in females' worldwide. Here, we attempted to evaluate the effect of DANCR on the biological behavior of transforming growth factor-ß (TGF-ß) stimulated ovarian cancer cells. MATERIAL AND METHODS The expression of DANCR in ovarian cancer cells (A2780 and SKOV3) treated with TGF-ß were detected by quantitative real-time polymerase chain reaction (qRT-PCR). DANCR silencing was constructed using lentiviral transfection in ovarian cancer cells. The Cell Counting Kit-8 (CCK-8), flow cytometry and Transwell assays were performed to measure some cytology index. Western blot was utilized to explore the effect of DANCR on Krüppel-like factor 5 (KLF5) expression. RESULTS The expression of DANCR in cancer cells (A2780 and SKOV3) treated with TGF-ß was significantly higher. DANCR silencing suppressed cell viability, migration and invasion, and induced cell apoptosis of TGF-ß treated ovarian cancer cells. Bioinformatics analysis showed that DANCR served as a sponge for miR-214, and also showed that KLF5 was targeted by miR-214. In addition, DANCR could inhibit the expression of KLF5. CONCLUSIONS We are the first to report that knockdown of DANCR could affect the biological process of ovarian cancer cells treated with TGF-ß by sponging miR-214, which may provide new therapeutic ideas of ovarian cancer.
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MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1α expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1α. Therefore, we inferred that there is a HIF-1α-miR-21 positive feedback loop through the PTEN/Akt/HIF-1α pathway in cervical cancer cells. In addition, we also demonstrated that miR-21 confers decreased autophagy in cervical cancer cells after IR via the Akt-mTOR signaling pathway. Decreased autophagy is one of the potential mechanisms of increased radioresistance in cervical cancer cells. These findings expand our understanding of radioresistance development in cervical cancer.
Assuntos
Autofagia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , MicroRNAs/fisiologia , PTEN Fosfo-Hidrolase/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Tolerância a Radiação , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Neoplasias do Colo do Útero/patologiaRESUMO
Low Impact Development Best Management Practices (LID-BMPs) have in recent years received much recognition as cost-effective measures for mitigating urban runoff impacts. In the present paper, a procedure for LID-BMPs planning and analysis using a comprehensive decision support tool was proposed. A case study was conducted to the planning of an LID-BMPs implementation effort at a college campus in Foshan, Guangdong Province, China. By examining information obtained, potential LID-BMPs were first selected. SUSTAIN was then used to analyze four runoff control scenarios, namely: pre-development scenario; basic scenario (existing campus development plan without BMP control); Scenario 1 (least-cost BMPs implementation); and, Scenario 2 (maximized BMPs performance). A sensitivity analysis was also performed to assess the impact of the hydrologic and water quality parameters. The optimal solution for each of the two LID-BMPs scenarios was obtained by using the non-dominated sorting genetic algorithm-II (NSGA-II). Finally, the cost-effectiveness of the LID-BMPs implementation scenarios was examined by determining the incremental cost for a unit improvement of control.
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Cidades , Conservação dos Recursos Naturais/métodos , Técnicas de Apoio para a Decisão , Drenagem Sanitária/métodos , Movimentos da Água , Qualidade da Água , China , Análise Custo-Benefício , Técnicas de Planejamento , ChuvaRESUMO
OBJECTIVE: To determine the survival rates of liver cancer in Qidong during the years 1972-2011, according to the data from a population-based cancer registry, in order to assess the long-term trends for prognosis of this cancer type. METHODS: The deadline of the last follow-up for survival status of the 28, 398 registered cases was April of 2012. Cumulative observed survival (OS) and relative survival (RS) rates were calculated using Hakulinen's method performed by the SURV3.01 software developed by the Finnish Cancer Registry. RESULTS: The 1-, 3-, 5-, 10-and 15-year OS rates were 15.18%, 6.23%, 4.26%, 2.79% and 2.39%, respectively; the 1-, 3-, 5-, 10-and 15-year RS rates were 15.47%, 6.60%, 4.69%, 3.41% and 3.29%, respectively. For males, these OS rates were 14.95%, 6.05%, 4.06%, 2.67% and 2.26%, and these RS rates were 15.23%, 6.41%, 4.47%, 3.26% and 3.12%, respectively. For females, these OS rates were 15.89%, 6.79%, 4.87%, 3.17% and 2.80%, and these RS rates were 16.20%, 7.20%, 5.37%, 3.87% and 3.82%, respectively. No statistical differences were found between the male and female groups (P>0.05). The 5-year RS rates for age groups 15-34, 35-44, 45-54, 55-64, 65-74 and 75+ years-old were 4.42%, 4.29%, 4.96%, 4.67%, 4.67% and 6.35%, and the 10-year RS rates were 3.17%, 2.98%, 3.44%, 3.47%, 3.75% and 11.27%, respectively. Remarkable improvement was seen for the 1-, 3-, 5-, 10-and 15-year OS rates in this setting since the 1980s. CONCLUSION: The survival outcome from Qidong registered cases with liver cancer has shown gradual progress over the past four decades. Early detection and improvement of therapies may be responsible for the improved prognosis of liver cancer. While the disparity gap of survival between this area and developed countries is narrowing, there is still a need for improving the survival in Qidong.
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Neoplasias Hepáticas , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Software , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
[This retracts the article DOI: 10.3892/ol.2018.8695.].
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Low impact development best management practices (LID-BMPs) are considered to be cost-effective measures for mitigating the water quantity and quality impact of urban runoff. Currently, there are many types of LID-BMPs, and each type has its own intrinsic technical and/or economical characteristics and limitations for implementation. The selection of the most appropriate BMP type(s) for a specific installation site is therefore a very important planning step. In the present study, a multi-criteria selection index system (MCIS) for LID-BMP planning was developed. The selection indexes include 12 first-level indices and 26 second-level indices which reflect the specific installation site characteristics pertaining to site suitability, runoff control performance, and economics of implementation. A mechanism for ranking the BMPs was devised. First, each individual second-level index was assigned a numeric value that was based on site characteristics and information on LID-BMPs. The quantified indices were normalized and then integrated to obtain the score for each of the first-level index. The final evaluation scores of each LID-BMP were then calculated based on the scores for the first-level indices. Finally, the appropriate BMP types for a specific installation site were determined according to the rank of the final evaluation scores. In order to facilitate the application of the MCIS BMP ranking system, the computational process has been coded into a software program, BMPSELEC. A case study demonstrating the MCIS methodology, using an LID-BMP implementation planning at a college campus in Foshan, Guangdong Province, is presented.
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Conservação dos Recursos Naturais/métodos , Poluição da Água/prevenção & controle , Benchmarking , Cidades , Drenagem Sanitária/métodos , Monitoramento Ambiental/métodosRESUMO
Silent information regulator 1 (SIRT1), a highly conserved NAD+-dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases. These evidences indicate that targeting SIRT1 has promising applications in the treatment of endocrine and metabolic diseases. This review focuses on the role of SIRT1 in endocrine and metabolic diseases. First, we describe the background and structure of SIRT1. Then, we outline the role of SIRT1 in endocrine and metabolic diseases such as hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, and polycystic ovarian syndrome. Subsequently, the SIRT1 agonists and inhibitors in the above diseases are summarized and future research directions are proposed. Overall, the information presents here may highlight the potential of SIRT1 as a future biomarker and therapeutic target for endocrine and metabolic diseases.
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Doenças do Sistema Endócrino , Doenças Metabólicas , Sirtuína 1 , Humanos , Histonas , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/tratamento farmacológico , Doenças do Sistema Endócrino/metabolismo , Biomarcadores/metabolismo , Terapia de Alvo MolecularRESUMO
BACKGROUND: With the development of sequencing technology, an increasing number of biomarkers have been identified in ovarian cancer (OC). However, there have been few comprehensive analyses of CRIP1 in patients with OC. METHODS: Logistic regression analysis was conducted to analyze the correlations between clinical characteristics and CRIP1 expression. Kaplan-Meier survival analysis was used to explore the difference in survival in each clinical subgroup. In addition, univariate and multivariate Cox regression analyses were further used to confirm the independent prognostic values of CRIP1. We further constructed ceRNA network based on the difference analysis. Subsequently, we used the ssGSEA algorithm to excavate the correlation between CRIP1 and tumor-infiltrating immune cells. Moreover, the potential biological functions of CRIP1 were investigated by gene function annotation. Finally, we knocked down CRIP1 gene for preliminary biological function verification in A2780 and SKOV-3 cell lines. RESULTS: The overexpression of CRIP1 was confirmed in The Cancer Genome Atlas (TCGA) cohort, immunohistochemistry, and OC cell lines. CRIP1 overexpression was correlated with the FIGO stage according to a logistic regression analysis that used the median of CRIP1 expression as a categorization of the dependent variable. Survival analysis revealed that CRIP1 was associated with a poor prognosis in most clinical subgroups and acts as an independent prognostic marker in OC patients. In immuno-bioinformatics analysis, CRIP1 is associated to majority of immune cells. This is noteworthy given that we identified that the ceRNA network based on CRIP1 may regulate progression in OC. In addition, gene enrichment analysis suggested CRIP1 may be involved in the JAK-STAT signaling pathway, etc. Finally, we found that knockdown CRIP1 could inhibit the proliferation of OC cells. CONCLUSION: We provided robust evidences that CRIP1 is an indicator of poor prognosis and a potential target for immunotherapy in patients with OC.
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Proteínas de Transporte/genética , Redes Reguladoras de Genes , Proteínas com Domínio LIM/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , RNA/genética , Linhagem Celular Tumoral , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Objective: This research is aimed at investigating the relationship between liver fibrosis in viral hepatitis and macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase (TIMP-1), and ceruloplasmin (CER) in serum level. Methods: Patients were randomly selected among those admitted to our hospital, and 60 healthy volunteers were chosen to serve as control participants. The levels of serum M-CSF, CER, and TIMP-1 were compared. According to the severity of their liver fibrosis, patients with CHB were separated into four groups: S1, S2, S3, and S4. Serum levels of M-CSF, CER, and TIMP-1 were correlated with liver fibrosis and hepatitis markers, and the diagnostic usefulness of the three indices was assessed with liver cirrhosis patients. Results: Increases in M-CSF and TIMP-1 in the CHB group but decreases in CER were statistically significant (P < 0.05). Serum levels of M-CSF, CER, TIMP-1, HA, PC-III, C-IV, and LN differed significantly across the four study groups (P < 0.05). Over time, as liver fibrosis worsened, we observed a progressive uptick in M-CSF, TIMP-1, LN, HA, C-IV, and PC-III levels and a progressive downtick in CER levels, with significant (P < 0.05) differences between the groups. There was a significant positive correlation between liver fibrosis and serum M-CSF, PC-III, TIMP-1, HA, LN, and C-IV levels in the CHB group (P < 0.05) and a significant negative correlation between serum CER and these same factors (P < 0.05). The AUC of 0.956 for diagnosing the S4 stage was greater than that of 0.857, 0.851, and 0.817 for M-CSF, CER, and TIMP-1, respectively. Conclusions: In CHB patients, the liver fibrosis degree is associated with the M-CSF, CER, and TIMP-1 levels, and the combined clinical detection of these three markers has better diagnostic significance.
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Hepatite Viral Humana , Inibidor Tecidual de Metaloproteinase-1 , Biomarcadores , Ceruloplasmina , Hepatite Viral Humana/complicações , Humanos , Fígado , Cirrose Hepática/diagnóstico , Fator Estimulador de Colônias de MacrófagosRESUMO
Circular RNAs (circRNAs) have been shown to be involved in the development of cancer. The aim of the present study was to investigate the role of circRNA SMARCA5 (cSMARCA5) in human cervical cancer. In the present study, cSMARCA5 expression was upregulated in cervical cancer tissues and cell lines. Furthermore, the proliferation rate of cells transduced with viral plasmids expressing small interfering RNA targeting cSMARCA5 was downregulated. Bioinformatics analysis predicted that microRNA (miR)432 targeted cSMARCA5, and miR432 was able to interact with epidermal growth factor receptor (EGFR) by binding to its 3'untranslated region. The expression levels of EGFR, ERK1 and ERK2 were increased in cervical cancer tissues. Furthermore, correlation analysis revealed that cSMARCA5 levels were positively correlated with ERK1 and ERK2 levels. In conclusion, the present findings suggested that cSMARCA5 may play an important role in the progression of cervical cancer via the ERK signaling pathway by modulating miR432.
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Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Circular/metabolismo , RNA Neoplásico/metabolismo , Neoplasias do Colo do Útero/metabolismo , Regiões 3' não Traduzidas , Feminino , Células HeLa , Humanos , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA Circular/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Long noncoding RNA lung cancer associated transcript 1 (LUCAT1) has been shown to be a lncRNA that facilitates the development and progression of several tumours. However, the evidence of LUCAT1 modulating the growth and metastasis of cervical cancer (CC) were still lacking. The present study aimed to explore the expression pattern, biological function and potential mechanism of LUCAT1 in CC. In this study, we, first, confirmed that LUCAT1 acted as an up-regulated lncRNA by analyzing the data from GCTA dataset and RT-PCR in both CC tissues and cell lines. We also showed that TINCR overexpression is induced by nuclear transcription factor SP1. Then, clinical assays showed that LUCAT1 was associated with advanced clinical progression and poor prognosis of CC patients. Importantly, multivariate Cox model confirmed that LUCAT1 expression was an independent prognostic factor for both 5-year overall survival in CC. Then, lost-function assays revealed that knockdown of LUCAT1 significantly suppressed CC cells proliferation, colony formation, migration, invasion and EMT by a series of cells experiments. Mechanistically, Bioinformatic tools predicted that miR-181a may target LUCAT1, which was confirmed using luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Overall, our findings showed that SP1-activated LUCAT1 exerts an oncogenic function in CC by binding to miR-181a, suggesting that miR-181a may be a ponderable and promising therapeutic target for CC.
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Movimento Celular/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/metabolismo , Regulação para Cima/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica , Prognóstico , Neoplasias do Colo do Útero/diagnósticoRESUMO
The current study was undertaken to investigate the potential influence of methylation on miR-362-5p/3p expression and further analyzed their independent prognostic value in cervical adenocarcinoma (ADC) and squamous cell carcinoma (SCC) respectively. SiHa and CaSki cells were used as the in vitro cell model. In silico bioinformatic analysis was conducted via the combined use of the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC), Starbase 3.0 and String 10.5. Results revealed that the downregulation of miR-362-5p/3p was accompanied by the infection of high-risk human papillomavirus (HR-HPV) and their expression was further decreased in HR-HPV cancer tissues. Demethylation could restore their expression. By performing Methylation-specific PCR (MSP) based on methylated or unmethylated specific primers, we confirmed that the proximal promoter region was methylated in both cell lines. Higher miR-362-3p expression might independently predict favorable overall survival (OS) in SCC patients (HR: 0.561, 95%CI: 0.354-0.889, p = 0.014), after adjustment of clinical stages, lymphovascular invasion and miR-362-5p expression. However, no prognostic value of miR-362-5p or miR-362-3p expression was observed in terms of OS in patients with ADC. Via bioinformatic analysis, we found that miR-362-3p might have an entirely different regulatory network in cervical ADC and SCC, which might help to explain the distinct prognostic value of miR-362-3p in these two histological subtypes. In summary, we infer that the methylation level of the proximal promoter region of pre-miR-362 would influence the expression of miR-362-5p/3p in cervical cancer. MiR-362-3p expression might be a specific prognostic biomarker in cervical SCC, but not in ADC.
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Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Neoplasias do Colo do Útero/genética , Carcinoma de Células Escamosas/mortalidade , Técnicas de Cultura de Células , Regulação para Baixo , Feminino , Humanos , Metilação , Prognóstico , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/mortalidadeRESUMO
Long non-coding RNAs (lncRNAs) have been identified as critical players in tumorigenesis. Previous studies revealed that lncRNA SBF2-AS1 was involved in tumor progression. However, the role and underlying mechanism of SBF2-AS1 in cervical cancer (CC) remain unknown. In the present study, our data showed that SBF2-AS1 expression was significantly increased in CC. High SBF2-AS1 expression was associated with advanced FIGO stage and lymph node metastasis of CC patients. Function assays showed that SBF2-AS1 inhibition significantly reduced CC cells proliferation both in vitro and in vivo. Mechanistically, we showed that SBF2-AS1 upregulation restrained the activity of miR-361-5p and led to overexpression of FOXM1 in CC cells. Furthermore, we found that miR-361-5p inhibitors could rescue the effects of SBF2-AS1 inhibition on CC cells proliferation. Taken together, we demonstrated that the SBF2-AS1/miR-361-5p/FOXM1 axis might play an important role in CC progression. SBF2-AS1 might serve as a potential therapeutic target for CC treatment.
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Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/genética , MicroRNAs/antagonistas & inibidores , Estadiamento de Neoplasias , RNA Longo não Codificante/antagonistas & inibidores , RNA Interferente PequenoRESUMO
The WRKY transcription factors, a large family of proteins in plants, are involved in multiple developmental and biological processes including response to phytohormones and abiotic stress. However, little information is available regarding the WRKY family in Eucalyptus, which has been the most widely planted hardwood trees in tropical and subtropical areas. In this study, a total of 79 WRKY genes (named as EgrWRKY1-79) were identified from the Eucalyptus grandis genome and classified into three main groups according to the phylogenetic analysis, which was further supported by their gene structure and conserved motifs. Of which, 28 EgrWRKYs were involved in tandem duplication but none for segmental duplication, indicating that tandem duplication was the main cause for the expansion of WRKY gene family in E. grandis. Subsequently, expression profiles of EgrWRKY genes in eight different tissues and in response to treatments of three hormones (SA, JA, and BR) and two abiotic stresses (salt and cold) were analyzed. The results revealed that the EgrWRKY genes had differential expression in their transcript abundance and they were differentially expressed in response to plant hormones and salt and cold stresses, suggesting their contributions to plant developmental processes as well as abiotic stresses with the involvement of hormone signaling transduction. Taken together, these findings will increase our understanding of EgrWRKY gene family involved in abiotic stresses and hormone signaling transduction, and also will provide some stress-responsive candidate EgrWRKY genes for further characterization of their functions in Eucalyptus.
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Eucalyptus/genética , Perfilação da Expressão Gênica/métodos , Reguladores de Crescimento de Plantas/farmacologia , Fatores de Transcrição/genética , Cromossomos de Plantas/genética , Eucalyptus/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genoma de Planta , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Estresse Fisiológico , Distribuição TecidualRESUMO
In the present study, the function of microRNA (miR)195 on abdominal aortic aneurysm (AAA) and its possible mechanism were investigated. Reverse transcriptionquantitative polymerase chain reaction analysis was used to detect the expression of miR195 in patients with AAA. The expression levels of miR195 in patients with AAA were effectively increased. The present study also used miR195 mimics to increase the expression of miR195, and ELISA kits and western blot analysis were used to analyze the levels of interleukin (IL)1ß and IL6, and the protein expression levels of matrix metalloproteinase (MMP)2, MMP9, tumor necrosis factor (TNF)α, nuclear factor (NF)κB, vascular endothelial growth factor (VEGF), phosphoinositide 3kinase (PI3K) and phosphorylated (p)Akt. The overexpression of miR195 promoted the levels of IL1ß and IL6, induced the protein expression of MMP2 and MMP9, upregulated the protein expression of TNFα and NFκB, and suppressed the protein expression levels of VEGF, PI3K and pAkt in angiotensin IIvascular smooth muscle cells. In addition, TNFα promoted the preinflammatory effect of miR195 on the protein expression levels of TNFα and NFκB, levels of IL1ß and IL6, and protein expression levels of MMP2 and MMP9 in the angiotensin IIvascular smooth muscle cells. Suppression of PI3K promoted the preinflammatory effect of miR195 on the protein expression of PI3K, pAkt and VEGF, the levels of IL1ß and IL6, and the protein expression of MMP2 and MMP9 in angiotensin IIvascular smooth muscle cells. Combined, these results suggested that miR195 suppressed AAA inflammation through the TNFα/NFκB and VEGF/PI3K/Akt pathways.
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Aneurisma da Aorta Abdominal/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Transdução de Sinais , Idoso , Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/patologia , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Masculino , MicroRNAs/imunologia , Pessoa de Meia-Idade , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
In this study, we aimed to assess the independent prognostic value of miR-361-3p in terms of overall survival (OS) and recurrence-free survival (RFS) in cervical cancer, as well as its possible regulative network. A retrospective analysis was performed by using data from the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC). Results showed that decreased miR-361-3p expression was associated with lymphovascular invasion and poor responses to primary therapy. The patients with recurrence and the deceased cases had substantially lower miR-361-3p expression compared to their respective controls. By generating Kaplan-Meier curves of OS and RFS, we found that high miR-361-3p expression was associated with better survival outcome. More importantly, univariate and multivariate analysis confirmed that high miR-361-3p expression was an independent indicator of favorable OS (HR: 0.377, 95% CI: 0.233-0.608, p < 0.001) and RFS (HR: 0.398, 95% CI: 0.192-0.825, p = 0.013). By performing bioinformatic analysis, we identified 24 genes that were negatively correlated with miR-361-3p expression. Among the potential targeting genes, SOST, MTA1, TFRC, and YAP1 are involved in some important signaling pathways modulating cervical cancer cell invasion, migration, and drug sensitivity. Therefore, it is meaningful to verify the potential regulative effect of miR-361-3p on the expression of these genes in the future.
Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Intervalo Livre de Doença , Feminino , Marcadores Genéticos/genética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores , Fatores de Transcrição , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Proteínas de Sinalização YAPRESUMO
Local and systemic metastasis is the main reason for the poor survival rate of patients with ovarian cancer (OC). MicroRNAs (miRNAs/miRs) are short non-coding RNAs that serve critical roles in the initiation and progression of OC. The present study demonstrated that expression of miR-19b was significantly increased in OC tissues and cell lines. Analysis of clinicopathological features revealed that the increased expression of miR-19b was associated with advanced International Federation of Gynecology and Obstetrics stage and lymphatic metastasis of OC patients. Loss-of-function experiments demonstrated that the silencing of miR-19b reduced the migration and invasion of OVCAR-3 cells; contrarily, the overexpression of miR-19b facilitated the migration and invasion of CAOV-3 cells. Furthermore, miR-19b regulated the expression of phosphatase and tensin homolog (PTEN) and the activity of the PTEN/RAC serine/threonine-protein kinase pathway in vitro. Notably, the results of dual-luciferase reporter assays indicated that PTEN was a direct downstream target of miR-19b in OC. Taken together, the results of the current study demonstrated that miR-19b serves an oncogenic role in the progression of OC, and could potentially act as a biomarker and therapeutic target for OC patients.