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Background and Objective: miR-22-3p functions as a tumor suppressor by targeting a variety of downstream genes, while its role and downstream targets in gastric cancer (GC) remain to be determined. We aimed to explore the role of miR-22-3p in gastric cancer and the potential mechanism. Methods: miR-22-3p mimic and inhibitor were used to overexpress or knockdown the expression of miR-22-3p separately. Quantitative real-time PCR (RT-qPCR) and Western blot were used to analyse the abundance of mRNA or protein level respectively. CCK-8 assay, cell colony formation assay, and flow cytometry were implemented to investigate the effect of miR-22-3p on gastric cancer cell proliferation and apoptosis. Luciferase assay was used to evaluate the role of miR-22-3p on the expression of glycolytic enzyme enolase 1 (ENO1). Results: In this study, we found that miR-22-3p was downregulated in GC cells. By transfecting the cells with miR-22-3p inhibitors or mimics, we showed that miR-22-3p suppressed GC cell proliferation and migration, as well as triggered cell death. In addition, we discovered that miR-22-3p was engaged in glycolysis by controlling the generation of lactate as well as the consumption of glucose. TargetScan database suggested that the ENO1 may be a target of the miR-22-3p, and the luciferase experiment verified this hypothesis. Recovery assays showed that the proliferation and migration of GC cells suppressed by miR-22-3p could be rescued by overexpression of ENO1. Conclusion: Collectively, we identified a new axis of miR-22-3p/ENO1 for GC development, which could be investigated as a therapeutic target for GC.
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MicroARNs , Neoplasias Gástricas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Línea Celular Tumoral , Proliferación Celular , Fosfopiruvato Hidratasa/genética , Proteínas de Unión al ADN , Biomarcadores de Tumor , Proteínas Supresoras de Tumor/genéticaRESUMEN
INTRODUCTION: Central lymph node status in papillary thyroid microcarcinoma (PTMC) plays an important role in treatment decision-making clinically, however, it is not easy to predict central lymph node metastasis (CLNM). The present work focused on finding the more rational alternative for evaluating central lymph node status while identifying influencing factors to construct a model to predict CLNM incidence. METHODS: In this study, we retrospectively analyzed the typical sonographic and clinicopathologic features of 546 PTMC patients who underwent surgery, among which, the data of 382 patients were recruited in the training cohort and that of 164 patients in the validation cohort. Based on the outcome of the training cohort, significant influencing factors were further identified through univariate analysis and were considered as independent variables in multivariable logistic regression analysis and incorporated in and presented with a nomogram. RESULTS: In total, six independent predictors, including the age, sex, tumor size, multifocality, capsular invasion, Hashimotos thyroiditis were entered into the nomogram. Both internal validation and external validation revealed the favorable discrimination of our as-constructed nomogram. Calibration curves exhibited high consistency. As suggested by decision-curve analyses, the as-constructed nomogram might be applied in clinic. Besides, the model also distinguished patients according to risk stratification. CONCLUSIONS: The novel nomogram containing remarkable influencing factors for CLNM cases was established in the present work. The nomogram can assist clinicians in clinical decision-making.
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Ganglios Linfáticos , Carcinoma Papilar , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la TiroidesRESUMEN
BACKGROUND MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. RESULTS Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. CONCLUSIONS miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroARNs/sangre , Adulto , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Metástasis Linfática , Masculino , MicroARNs/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Curva ROCRESUMEN
BACKGROUND Colorectal cancer (CRC) mainly refers to colon and rectum cancer, which is the most common gastrointestinal malignant tumor. MicroRNAs (miRNAs) in tumors participate in multiple processes of malignancy development, including cell differentiation, proliferation, invasion, and metastasis. In this study we explored the relationship of miR-1260b abnormal expression with clinical pathological features in CRC patients. MATERIAL AND METHODS The expression of miR-1260b was detected by real-time quantitative polymerase chain reaction (real-time PCR) in 120 cases of CRC tissues. The correlation of miR-1260b expression with the clinicopathologic features of CRC was analyzed by SPSS 21.0 statistical software. The Kaplan-Meier method was used for survival analysis. Cox regression analyses were conducted to determine whether miR-1260b was an independent predictor of survival for CRC patients. RESULTS The miR-1260b expression in CRC was significantly higher than the expression levels in the corresponding para-carcinoma tissues (P<0.001). According to the expression levels of miR-1260b, 120 cases of CRC patients were classified into either the miR-1260b high expression group or the miR-1260b low expression group. The high expression levels of miR-1260b in CRC patients was associated with lymph node metastasis (P<0.05) and venous invasion (P<0.001). However, the high miR-1260b expression had no significant correlation with other clinical parameters (P>0.05). The high miR-1260b expression patients survived for shorter times than those CRC patients with low miR-1260b expression (P<0.05). Multivariate analysis revealed that high miR-1260b means poor prognosis of patients with CRC. CONCLUSIONS The high expression level of miR-1260b is an independent prognostic biomarker that indicates a worse prognosis for patients with CRC.
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Neoplasias Colorrectales/genética , MicroARNs/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de SupervivenciaRESUMEN
BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC.
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Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Técnica del Anticuerpo Fluorescente/métodos , Células Neoplásicas Circulantes/patología , Adulto , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Inmunohistoquímica/métodos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) for patients with gastric cancer. METHODS: Electronic databases including PUBMED, EMBASE, and Cochrane Library were retrieved for original studies from their inception to April 2014. Two reviewers independently evaluated the quality of the included studies and extracted the data. All Statistical analyses were performed using RevMan Version 5.2 software. RESULTS: Six randomized controlled trials involving 1,171 patients were included. The meta-analysis showed that there were statistical significances between chemoradiotherapy group and chemotherapy group in 5-year disease free survival rate (OR = 1.56, 95% CI: 1.09-2.24), local-regional recurrence rate (OR = 0.46, 95% CI: 0.32-0.67) and neutropenia (OR = 1.47, 95% CI: 1.11-1.96). While treatment efficacy did not differ significantly by the 5-year overall survival rate (OR = 1.32, 95% CI: 0.92-1.88), 3-year disease free survival rate (OR = 1.28, 95% CI: 0.92-1.80), and new metastases (OR = 0.76, 95% CI: 0.57-1.03). Toxicities were not significantly different between two groups for nausea/vomiting, diarrhea, anemia, and thrombocytopenia. CONCLUSIONS: For patients with gastric cancer, adjuvant chemoradiotherapy could significantly improve 5-year disease free survival rate and reduce local-regional recurrence rate compared with chemotherapy and, can be well accepted and tolerated.
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Neoplasias Gástricas/terapia , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Humanos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The objective of the present meta-analysis was to estimate the magnitude of survival benefits of neoadjuvant chemotherapy (NAT) in resectable cancer of the gastric and gastroesophageal junction. MATERIALS AND METHODS: We searched PubMed, Embase, the Cochrane Library, ISI Web of Knowledge, Chinese biomedical literature database, Chinese Scientific Journals full-text database of retrieved articles from their inception to 2013. Two reviewers independently retrieved study and data extraction of included studies. Results regarding the overall survival and progression-free survival in the meta-analysis were expressed as hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Twelve randomized control trials (n=1755) were eligible for final meta-analysis. NAT was associated with a statistically significant benefit in terms of overall survival (HR=0.72; 95% CI, 0.56-0.93, P=0.01), progression-free survival (HR=0.73; 95% CI, 0.62-0.87, P=0.0003), 5-year survival rate [relative risk (RR)=1.36; 95% CI, 1.10-1.67, P=0.0004], and curative resection rate (RR=1.11; 95% CI, 1.03-1.20, P=0.009). Five-year survival rate increased from 30% to 42% with NAT. No significant difference with regards to overall postoperative complications rate (RR=1.08; 95% CI, 0.92-1.27, P=0.28) was found between 2 groups. CONCLUSION: There is convincing evidence for a survival benefit of NAT over surgery alone in patient with cancer of the gastric and gastroesophageal junction.
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Antineoplásicos/uso terapéutico , Unión Esofagogástrica , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Quimioterapia Adyuvante/mortalidad , Supervivencia sin Enfermedad , Unión Esofagogástrica/cirugía , Humanos , Terapia Neoadyuvante/mortalidad , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/mortalidad , Tasa de SupervivenciaRESUMEN
Numerous studies examined the association between excision repair complementation group 1 (ERCC1) expression and the prognosis of gastric cancer patients receiving platinum-based chemotherapy but yielded controversial results. We thus conducted a meta-analysis to quantitatively evaluate the prognostic value of ERCC1 expression in gastric cancer patients receiving platinum-based chemotherapy. A systematic literature search was performed to identify relevant studies in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Database up to December 17, 2013. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated. Moreover, meta-regression analysis and subgroup analysis were conducted according to ethnicity, HR extraction, detection methods, survival analysis, and quality score. A total of 1,409 patients from 21 studies were subjected to final analysis. Positive/high ERCC1 expression was significantly associated with poorer overall survival (HR, 1.58; 95 % CI, 1.09-2.28), especially in Asians (HR, 1.81; 95 % CI, 1.20-2.73), and lower response rate (OR, 0.26; 95 % CI, 0.18-0.36), but not with clinicopathological features, such as gender (OR, 1.01; 95 % CI, 0.68-1.51), grade (OR, 0.66; 95 % CI, 0.43-1.01), and stage (OR, 1.05; 95 % CI, 0.58-1.90). This meta-analysis suggested that ERCC1 expression might be a useful biomarker to predict response and survival for gastric cancer patients receiving platinum-based chemotherapy, particularly in Asians.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Humanos , Inmunohistoquímica , Oportunidad Relativa , Platino (Metal)/administración & dosificación , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay. Further mechanism was explored that the transcription factor HNF1A regulated the expression of EPS8 and downstream signaling pathways by directly binding to the promoter region of EPS8. Our comprehensive analysis of clinical samples in this study showed that upregulated expression of HNF1A was associated with poor survival in GBM patients. Further, we found that knockdown of HNF1A markedly suppressed the malignant phenotype of GBM cells in vivo and in vitro as well as promoted apoptosis of tumor cells, which was reversed by upregulation of HNF1A. Mechanistically, HNF1A could significantly activate PI3K/AKT signaling pathway by specifically binding to the promoter regions of EPS8. Moreover, overexpression of EPS8 was able to reverse the apoptosis of tumor cells caused by HNF1A knockdown, thereby exacerbating the GBM progression. Correctively, our study has clarified the explicit mechanism by which HNF1A promotes GBM malignancy and provides a new therapeutic target for further clinical application.
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Glioblastoma , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Glioblastoma/genética , Glioblastoma/patología , Ratones Desnudos , Proliferación Celular , Línea Celular Tumoral , Transducción de Señal , Factores de Transcripción/metabolismo , Regulación Neoplásica de la Expresión Génica , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.
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BACKGROUND: The objective of the present meta-analysis was to estimate the magnitude of survival and recurrence free benefits from different lymphadenectomy in patients with resectable gastric cancer. METHODS: A comprehensive search was performed for original studies published from their inception to 2012. Two reviewers independently assessed search results, methodological quality, and data extraction of included studies. Results regarding the overall survival (OS) and recurrence free survival (RFS) in the meta-analysis were expressed as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Twelve randomized control trials (RCTs) were eligible for final meta-analysis. There was not significant difference in OS between D1 and D2 lymphadenectomy (HR = 0.92, 95% CI: 0.77-1.10, P = 0.36), but subgroup analysis of patients without splenectomy and/or pancreatectomy has a trend for OS much more benefiting D2 compared to D1 patients. A significant RFS improvement was found in favor of D2 lymphadenectomy, sensitivity analysis also gives similar fixed effect estimates (HR = 0.68, 95% CI: 0.58-0.81, P = 0.84). There were no significant differences in OS and RFS between D2 group and D3 group (1 trial). CONCLUSIONS: The present meta-analysis indicates that D2 lymphadenectomy with spleen and pancreas preservation offers the most survival benefit for patients with gastric cancer when done safety.
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Gastrectomía/métodos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Pancreatectomía , Esplenectomía , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: We carry out a meta-analysis to evaluate the effectiveness and safety of laparoscopy-assisted gastrectomy (LAG) versus open gastrectomy for resectable gastric cancer. METHODS: We searched EMBASE, the Cochrane Library, PubMed, Science Citation Index (SCI), Chinese biomedicine literature database to identify randomized controlled trials (RCTs) from their inception to April 2012. Meta-analyses were performed using RevMan 5.0 software. It was in line with the preferred reporting items for systematic reviews and meta-analyses statement. The quality of evidence was assessed by GRADEpro 3.6. RESULTS: Eight RCTs totaling 784 patients were analyzed. Compared with open gastrectomy group, no significant differences were found in postoperative mortality (OR = 1.49; 95 % CI 0.29-7.79), anastomotic leakage (OR = 1.02; 95 % CI 0.24-4.27) , overall mean number of harvested lymph nodes [weighed mean difference (MD) = -3.17; 95 % CI -6.39 to 0.05]; the overall postoperative complication morbidity (OR = 0.54; 95 % CI 0.36-0.82), estimated blood loss (MD = -107.23; 95 % CI -148.56 to -65.89,) frequency of analgesic administration (MD = -1.69; 95 % CI -2.18 to -1.21, P < 0.00001), incidence of pulmonary complications (OR = 0.43, 95 % CI 0.20-0.93, P = 0.03) were significantly less in LAG group; LAG had shorter time to start first flatus (MD = -0.23; 95 % CI -0.41 to -0.05) and decreased hospital stay (MD = -1.72; 95 % CI -3.40 to 0.04), but, LAG still had longer operation time (MD = 76.70; 95 % CI 51.54-101.87). CONCLUSIONS: On the basis of this meta-analysis we conclude that although LAG was still a time-consuming and technically dependent procedure, it has the advantage of better short-term outcome. Long term survival data from other studies are urgently needed to estimate the survival benefit of this technique.
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Gastrectomía/métodos , Laparoscopía , Neoplasias Gástricas/cirugía , Analgésicos/uso terapéutico , Fuga Anastomótica , Pérdida de Sangre Quirúrgica , Utilización de Medicamentos , Humanos , Tiempo de Internación , Escisión del Ganglio Linfático , Tempo Operativo , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Investigating the role of ubiquitin-specific peptidase 10 (USP10) in triple-negative breast cancer (TNBC). Analyzed USP10 expression levels in tumors using public databases. Detected USP10 mRNA and protein levels in cell lines. Examined USP10 expression in tumor tissues from breast cancer patients. Conducted USP10 knockdown experiments and analyzed changes in cell proliferation and metastasis. Confirmed protein-protein interactions with USP10 through mass spectrometry, Co-IP, and fluorescence experiments. Assessed impact of USP10 on transcription factor 4 (TCF4) ubiquitination and validated TCF4's influence on TNBC cells. We initially identified a pronounced overexpression of USP10 across multiple tumor types, including TNBC. Subsequently, we observed a conspicuous upregulation of USP10 expression levels in breast cancer cell lines compared to normal breast epithelial cells. However, upon subsequent depletion of USP10 within cellular contexts, we noted a substantial attenuation of malignant proliferation and metastatic potential in TNBC cells. In subsequent experimental analyses, we elucidated the physical interaction between USP10 and the transcription factor TCF4, whereby USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC. Collectively, this study demonstrates that USP10 facilitated the deubiquitination modification of TCF4, consequently promoting its protein stability and contributing to the initiation and progression of TNBC.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismo , Ubiquitinación , Células Epiteliales/metabolismo , Regulación hacia Arriba , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Ubiquitina Tiolesterasa/genéticaRESUMEN
Background: Glioma is a prevalent primary brain cancer with high invasiveness and typical local diffuse infiltration. Alternative splicing (AS), as a pervasive transcriptional regulatory mechanism, amplifies the coding capacity of the genome and promotes the progression of malignancies. This study was aimed at identifying AS events and novel biomarkers associated with survival for glioma. Methods: RNA splicing patterns were collected from The Cancer Genome Atlas SpliceSeq database, followed by calculating the percentage of splicing index. Expression profiles and related clinical information of glioma were integrated based on the UCSC Xena database. The AS events in glioma were further analyzed, and glioma prognosis-related splicing factors were identified with the use of bioinformatics analysis and laboratory techniques. Further immune infiltration analysis was performed. Results: Altogether, 9028 AS events were discovered. Upon univariate Cox analysis, 425 AS events were found to be related to the survival of patients with glioma, and 42 AS events were further screened to construct the final prognostic model (area under the curve = 0.974). Additionally, decreased expression of the splicing factors including Neuro-Oncological Ventral Antigen 1 (NOVA1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), heterogeneous nuclear ribonucleoprotein L-like protein (HNRNPLL), and RNA-Binding Motif Protein 4 (RBM4) contributed to the poor survival in glioma. The immune infiltration analysis demonstrated that AS events were related to the proportion of immune cells infiltrating in glioma. Conclusions: It is of great value for comprehensive consideration of AS events, splicing networks, and related molecular subtype clusters in revealing the underlying mechanism and immune microenvironment remodeling for glioma, which provides clues for the further verification of related therapeutic targets.
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Empalme Alternativo , Glioma , Biomarcadores de Tumor/genética , Análisis de Datos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Glioma/genética , Humanos , Pronóstico , Factores de Empalme de ARN/genética , Proteínas de Unión al ARN/genética , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVE: The objectives of this review are to compare the effectiveness and safety of radiochemotherapy (RTCT) with radiotherapy (RT) alone in locally advanced cervical cancer (LACC). DATA SOURCES: We comprehensively searched the Cochrane library, Medline, EMBASE, Chinese biomedicine literature database, Chinese scientific full-text database and Chinese journal full-text database for relevant articles. The computer search was supplemented with a manual search of reference lists for all available review articles. Also reference lists of the included studies were reviewed. RESULTS: We included 18 randomized trials involving 3,517 patients. Meta-analysis results are as follows: the response rate, 3 and 5-year survival rates were significantly better in patients in the RTCT group than in RT group. As adverse effects, limited evidence suggests that there was no significant difference between the two groups with regard to rectitis, cystitis, nausea and vomiting. But RTCT group has higher incidence rates than RT group in gastrointestinal, myelosuppression and leucopenia. CONCLUSION: The combination of radiotherapy and chemotherapy was more effective for LACC than radiotherapy alone. There was no significant difference between the RTCT regimen group and RT regimen group with regard to adverse effects.
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Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma/mortalidad , Terapia Combinada/métodos , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidadRESUMEN
Hepatocellular carcinoma (HCC) is the most common digestive system cancer. In the current study, we investigated the biological effects of Ras-related protein Rap-2a (RAP2A), a GTPase protein, in HCC tissues and cells. We found that RAP2A was upregulated in HCC tissues and cells. RAP2A knockdown could effectively inhibit the proliferation of HCC cells and weaken its apoptosis resistance. In terms of its action mechanism, RAP2A may be involved in activating the mTOR signaling pathway. Therefore, we believe that RAP2A is abnormally highly expressed in HCC tissues and promotes tumor cell proliferation and apoptosis resistance by activating the mTOR signaling pathway, and it may serve as a potential target for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Unión al GTP rapRESUMEN
We recently read with interest the article "Diagnostic approach to faecal incontinence: What test and when to perform?". This is a comprehensive and practical review, which has particular significance for guiding clinicians to improve the examination strategy. Although we appreciate their work very much, based on the in-depth analysis of this research, we found some detailed problems in the article and will give our comments in this letter. If the author can further improve the relevant research, it will be valuable.
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Incontinencia Fecal , Canal Anal , Incontinencia Fecal/diagnóstico , Humanos , ManometríaRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression. METHODS: CircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments. RESULTS: Circ-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression. CONCLUSION: The circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.
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Several studies have evaluated the possible association between antioxidants vitamins or selenium supplement and the risk of prostate cancer, but the evidence is still inconsistent. We systematically searched PubMed, EMBASE, the Cochrane Library, Science Citation Index Expanded, Chinese biomedicine literature database, and bibliographies of retrieved articles up to January 2009. We included 9 randomized controlled trials with 165,056 participants; methodological quality of included trials was generally high. Meta-analysis showed that no significant effects of supplementation with beta-carotene (RR 0.97, 95% CI 0.90-1.05) (3 trials), vitamin C (RR 0.98, 95% CI 0.91-1.06) (2 trials), vitamin E (RR 0.96, 95% CI 0.85-1.08) (5 trials), and selenium (RR 0.78, 95% CI 0.41-1.48) (2 trials)versus placebo on prostate cancer incidence. The mortality of prostate cancer did not differ significantly by supplement of beta-carotene (RR 1.19, 95% CI 0.87 -1.65) (1 trial), vitamin C (RR 1.45, 95%CI 0.92-2.29) (1 trial), vitamin E (RR 0.85, 95%CI 0.58-1.24) (2 trials), and selenium (RR 2.98, 95% CI 0.12-73.16) (1 trial). Our findings indicate that antioxidant vitamins and selenium supplement did not reduce the incidence and mortality of prostate cancer, these data provide no support for the use of these supplements for the prevention of prostate cancer.