RESUMO
Choroid plexus papilloma (CPP) is a rare benign intracranial tumor origin that predominantly manifests in the lateral ventricle in children, accounting for 0.3%-0.6% of all primary intracranial tumors. It is extremely rare to have the CPP in the trigone of the lateral ventricle through the contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA). Herein, we report this rare case. A 7-year-old girl presented with headache. Magnetic resonance imaging of the brain showed periatrial lesions, and histopathological examination confirmed CPP (WHO grade I). The contralateral PITTA is a safe, effective, reasonable, and appropriate for some lesions in the trigone of the lateral ventricle. It provides a wider surgical angle (especially for the lateral extension) and reduces the risk of disturbance of the optic radiation compared with the conventional approaches. The use of multiple modern neurosurgical techniques, including interventional embolization, intraoperative navigation, microscope, and electrophysiological monitoring, make the procedure much easier and more accurate, and the neuroendoscope adds to the visualization of the microscope and can reduce surgical complications.
RESUMO
Our understanding of the DNA damage responses of human cells to radiation has increased remarkably over the recent years although some notable signaling events remain to be discovered. Here we provide a brief account of the key molecular events of the responses to reflect the current understanding of the key underlying mechanisms involved.
RESUMO
BACKGROUND: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. METHODS: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. RESULTS: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. CONCLUSION: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.
Assuntos
Neoplasias Colorretais , Nomogramas , Humanos , Reprodutibilidade dos Testes , Prognóstico , Estresse do Retículo Endoplasmático/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapiaRESUMO
Cellular communication between gastric cancer (GC) cells with different metastatic potentials and microenvironments and resultant cancer progression is not fully understood. Circular RNAs (circRNAs) and exosomal circRNAs are known to play extremely important regulatory roles in GC occurrence and progression. Here, we revealed significant differences in coronin-like actin-binding protein 1C (CORO1C) derived circRNA hsa_circ_0000437 between GC and para-cancer tissues. Hsa_circ_0000437 regulated GC cell proliferation, invasion, migration and apoptosis by targeting Ser/Arg-rich splicing factor 3 (SRSF3) and inhibiting programmed cell death 4 (PDCD4). The ectopic expression of hsa_circ_0000437 dramatically promoted tumor growth in nude mice in vivo. Furthermore, both gain-of-function and loss-of-function experiments demonstrated that hsa_circ_0000437 promoted human lymphatic endothelial cells (HLECs) invasion, migration, and tube formation in vitro and also promoted lymphangiogenesis and lymph node metastasis (LNM) in popliteal LNM model in vivo, when it was enriched in GC-secreted exosomes and transferred into HLECs. Mechanistically, exosomal hsa_circ_0000437 induced LNM via HSPA2-ERK signaling pathway independent of VEGF-C. Clinical data showed that exosomal hsa_circ_0000437 was enriched in the serum of GC patients, which was associated with LNM. In summary, these findings highlight the potential role of hsa_circ_0000437 as an outcome biomarker in GC patients with LNM, which may provide a novel target for GC therapy.
Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Processamento de RNA/genética , RNA Circular/genética , Proteínas de Ligação a RNA , Fatores de Processamento de Serina-Arginina/genética , Neoplasias Gástricas/patologia , Microambiente Tumoral , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
MicroRNAs (miRNAs) participate in the formation of multiple diseases, including gastric cancer (GC), through modulating specific targets. Here, we explored the functions and regulatory mechanisms of miR-205-5p in GC. MiR-205-5p levels were detected in GC cells through qRT-PCR. Besides, the role of miR-205-5p in cell proliferation, cell apoptosis, cell cycle, cell invasion, and metastasis was assessed through CCK-8 assay, colony formation, flow cytometry, scratch assay, transwell, and western blot. Moreover, the Starbase website was used to predict the target gene of miR-205-5p, further verified by a dual-luciferase reporter assay. Furthermore, the functional effects of the family with sequence similarity 84 member B (FAM84B) on GC mediated by miR-205-5p upregulation were further investigated. MiR-205-5p expression was decreased in GC cells. Upregulation of miR-205-5p inhibited cell proliferation and metastasis and induced apoptosis and cycle arrest of GC cells. Moreover, FAM84B was predicted and confirmed as a target of miR-205-5p and negatively related to miR-205-5p. Mechanically, FAM84B overexpression partially rescued the functional effects of miR-205-5p upregulation on GC cell progression. This study suggests the potential of miR-205-5p/FAM84B as novel targets for the treatment of GC.
RESUMO
Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.
RESUMO
BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/fisiologia , Tuberculose Pulmonar/diagnóstico , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Tuberculose Latente/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Tuberculose Pulmonar/terapiaRESUMO
BACKGROUND: Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. MATERIALS AND METHODS: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777, 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658, 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. CONCLUSIONS: SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings.
RESUMO
OBJECTIVE: Our study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies. DESIGN: Meta-analysis. DATA SOURCES: Relevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE. ELIGIBILITY CRITERIA: All published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included. DATA EXTRACTION AND SYNTHESIS: Studies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated. RESULTS: A total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07). CONCLUSIONS: Pretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.
Assuntos
Volume Plaquetário Médio , Neoplasias Gástricas , Humanos , Prognóstico , Intervalo Livre de Progressão , Curva ROCRESUMO
This study explored the effect of methyl-indole on pancreatic cancer cell viability and investigated the mechanism involved. The viability of pancreatic cells showed a significant suppression on treatment with methyl-indole in dose-based manner. Treatment with 5 µM methyl-indole suppressed Capan-1 cell viability to 23%. The viability of Aspc-1 cells was reduced to 20% and those of MIApaCa-2 cells to 18% by 5 µM methyl-indole. The apoptotic proportion of Capan-1 cells was 67%, while as those of Aspc-1 and MIApaCa-2 cells increased to 72 and 77%, respectively, on treatment with 5 µM methyl-indole. The level of P13K, p-Tyr, p-Crkl and p-Akt was inhibited in the cells by methyl-indole. Moreover, methyl-indole also suppressed zinc-finger protein, X-linked mRNA and protein expression in tested cells. In summary, methyl-indole exhibits anti-proliferative effect on pancreatic cancer cells and induces apoptosis. It targeted ZFX expression and down-regulated P13K/AKT pathway in pancreatic cancer cells. Therefore, methyl-indole acts as therapeutic agent for pancreatic cancer and may be studied further.
RESUMO
Studies have shown that long non-coding RNAs (lncRNAs) play vital roles in the development of cancer, including colorectal cancer (CRC). Our purpose is to validate the diagnostic value of serum differentiation antagonizing non-protein coding RNA (DANCR) in CRC by focusing on its expression and clinical application. lncRNA expression profiles of CRC patients were obtained and analyzed by repurposing the publically available microarray data. Tissue or serum specimens were obtained from 40 patients with primary CRC, 10 patients with recurrent CRC, 40 patients with colorectal polyps, and 40 healthy controls. It was found that DANCR level in the CRC tissue and serum was significantly increased, and serum DANCR expression was decreased in post-operative patients as compared with that in pre-treatment patients and recurrent patients. In addition, serum DANCR expression was significantly correlated with different TNM stages. Correlation analysis of DANCR and other diagnostic indicators showed that the serum DANCR expression level was significantly correlated with CA199 but not with CEA in CRC patients. As for diagnostic efficiency by ROC analysis, the area under the curve (AUC) of serum DANCR was higher than that of CEA and CA199 in CRC group vs. colorectal polyp group. Simultaneous detection of DANCR, CEA and CA199 yielded the highest sensitivity and AUC as compared with either of them alone. Taken together, serum DANCR was up-regulated in CRC patients and high expression of DANCR may prove to be a potential biomarker for the diagnosis of CRC.
Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , China , Neoplasias Colorretais/diagnóstico , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/sangue , Curva ROCRESUMO
BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant diseases and is the third leading cause of cancer-related death. This study aimed to investigate the effect of hydroxypyridinone-coumarin (HPC) on MHCC97 and HepG2 human HCC cells and the mechanisms involved. MATERIAL AND METHODS MHCC97 and HepG2 human HCC cells were cultured in vitro. An MTT cytotoxicity assay was used to assess cell viability and proliferation, with and without treatment with HPC. Cell autophagosomes were labeled with GFP-LC3 using confocal fluorescence microscopy. Western blot was used to measure protein expression. RESULTS HPC significantly reduced the cell proliferation rate in a concentration-dependent manner, with 2 µM of HPC resulting in a reduced proliferation rate of MHCC97 cells (by 36%) and HepG2 cells (by 29%) (P<0.02). HPC significantly reduced autophagy in MHCC97 and HepG2 cells. Western blot showed that treatment with HPC significant upregulated Atg5, beclin-1, LC3-phosphatidylethanolamine conjugate (LC3-II), and Atg-3, reduced p62 and Akt protein expression, and induced phosphorylation of ERK1/2. GFP-LC3B labeling in MHCC97 and HepG2 cells was increased following HPC treatment. CONCLUSIONS HPC induced autophagy and inhibited the proliferation of MHCC97 and HepG2 HCC cells in vitro and involved activation of ERK1/2 and down-regulation of the Akt pathway.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Cumarínicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Piridonas/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Cumarínicos/química , Cumarínicos/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação/efeitos dos fármacos , Piridonas/química , Piridonas/uso terapêuticoRESUMO
Early diagnosis of gastric cancer (GC) is an effective method to improve prognosis. Increasing number of long noncoding RNAs (lncRNAs) have been reported as biomarkers for several cancers. We aim to detect the level of lncRNA B3GALT5-AS1 and its association with clinical parameters and to further explore its application value in GC. We measured serum B3GALT5-AS1 expression in 107 patients with GC, 40 polyp patients, and 87 normal controls to explore the significance of serum B3GALT5-AS1 in GC using the quantitative real-time polymerase chain reaction method. The result demonstrated that B3GALT5-AS1 level was markedly richer in GC patients than that in normal people (P < .001). B3GALT5-AS1 may be served as a diagnostic marker for distinguishing GC patients from healthy people, and the proportion under the receiver operating characteristics curve is 0.816 (95% confidence interval, 0.758-0.874; P = .03). Further exploration validated that high serum B3GALT5-AS1 level was related to TNM stage (P = .024), and lymph node metastasis (P = .023). Our study suggested that serum B3GALT5-AS1 may be employed as an ideal biomarker for early screening of GC.
Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Galactosiltransferases/genética , Gastrectomia/mortalidade , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Antissenso/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
Long noncoding RNAs (lncRNAs) have increasingly been found to be key mediators of tumor biology and to have potential diagnostic value as biomarkers of particular forms of cancer. TUG1 (taurine-upregulated gene 1) is an lncRNA that has been found to be upregulated in a range of different cancer types, but levels of its expression in the serum of patients with multiple myeloma (MM) are uncertain, as is its diagnostic relevance in such a population. This study therefore explored whether TUG1 levels in patient serum serve as a diagnostic biomarker of MM. We analyzed serum TUG1 levels via quantitative real-time polymerase chain reaction in healthy control and MM patient serum and observed clear TUG1 upregulation in MM patients (p < 0.001). We further found that the levels of TUG1 in patient serum correlated with factors including disease clinical stage, ß2-microglobulin, total protein, albumin, globulin, and bone injury (p < 0.05), suggesting that this lncRNA may be independently predictive of MM disease stage. We found areas under receiver operating characteristic curves as high as 0.792 (p < 0.001) for TUG1-a value higher than that for either ß2-microglobulin (0.747) or albumin (0.597)-with the combination of all three biomarkers improving diagnostic specificity and areas under the curve of 96.9% and 0.836, respectively (p < 0.001). Together, our results suggest that serum TUG1 levels may serve as a valuable biomarker that can help to facilitate MM diagnosis.
Assuntos
Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo , RNA Longo não Codificante/sangue , RNA Neoplásico/sangue , Regulação para Cima , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnósticoRESUMO
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC. METHODS: Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC. RESULTS: A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone-mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC. CONCLUSION: Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Biologia Computacional/métodos , Ciclina B1/genética , Ciclina B1/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Mapas de Interação de Proteínas/genética , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/uso terapêutico , Taxa de SobrevidaRESUMO
MicroRNAs (miRNA/miRs) have been demonstrated to be critical posttranscriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR145 was decreased in EOC tissues and cell lines. Overexpression of miR145 inhibited the proliferation, migration and invasion of EOC cells. The Dtype cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR145. Collectively, the results indicated that miR145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR145 was suggested to be a potential miRNAbased therapeutic target in ovarian cancer.
Assuntos
Ciclina D2/genética , Fator de Transcrição E2F3/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Interferência de RNA , Regiões 3' não Traduzidas , Adulto , Idoso , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Genes Reporter , Humanos , Pessoa de Meia-IdadeRESUMO
Endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) has an important role in the pathogenesis of Crohn's disease (CD). FK506 binding protein 11 (FKBP11), a member of the peptidylprolyl cistrans isomerase family, is involved in the unfolded protein response (UPR) and is closely associated with inflammation. Previous bioinformatics analysis revealed a potential association between FKBP11 and human CD. Thus, the present study aimed to investigate the potential significance of FKBP11 in IEC homeostasis and CD. In the present study, increased expression of FKBP11 was detected in the intestinal inflammatory tissues of patients with CD. Furthermore, the results of the present study revealed that overexpression of FKBP11 was accompanied by increased expression levels of the ER stress marker 78 kDa glucoseregulated protein in the colon tissues of a 2, 4, 6trinitrobenzenesulphonic acidinduced mouse colitis model. Using interferonγ (IFNγ)/tumor necrosis factorα (TNFα)stimulated IECs as an ER stress and apoptosis cell model, the associated of FKBP11 with ER stress and apoptosis levels was confirmed in IECs. Overexpression of FKBP11 was revealed to significantly attenuate the elevated expression of proapoptotic proteins (Bcl2 associated X apoptosis regulator, caspase12 and active caspase3), suppress the phosphorylation of cJun Nterminal kinase (JNK), and decrease apoptosis of IFNγ/TNFα stimulated IECs. Knockdown of FKBP11 by transfection with small interfering RNA further validated the aforementioned results. In conclusion, these results suggest that the UPR protein FKBP11 may protect IECs against IFNγ/TNFα induced apoptosis by inhibiting the ER stressassociated JNK/caspase apoptotic pathway in CD.
Assuntos
Colite/genética , Doença de Crohn/genética , Inflamação/genética , Proteínas de Ligação a Tacrolimo/genética , Animais , Apoptose/genética , Caspases/genética , Colite/induzido quimicamente , Colite/patologia , Doença de Crohn/patologia , Estresse do Retículo Endoplasmático/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interferon gama/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , MAP Quinase Quinase 4/genética , Camundongos , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/genéticaRESUMO
Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas de Ligação ao GTP/metabolismo , Neoplasias Hepáticas/metabolismo , Niacinamida/análogos & derivados , Proteínas Nucleares/metabolismo , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/farmacologia , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sorafenibe , Taxa de Sobrevida , Regulação para Cima , Adulto Jovem , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients.
Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas de Ciclo Celular/biossíntese , Proliferação de Células , Neoplasias da Vesícula Biliar , Proteínas de Neoplasias/biossíntese , Transativadores/biossíntese , Idoso , Idoso de 80 Anos ou mais , Animais , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
MgCl2-supported titanium Ziegler-Natta catalyst containing CO2-based poly(propylene ether carbonate) diols as a potential internal electron donor (IED) was synthesized and employed for 1-butene polymerization. When compared with the Ziegler-Natta catalyst using poly(polypropylene glycol) as IED, the catalyst prepared with poly(propylene ether carbonate) diols showed good particle morphology, higher activity and stereoselectivity. The results suggested that existence of the carbonate group within the structure of poly(propylene ether carbonate) diols truly plays an important role in improving the performance of the catalyst for the 1-butene polymerization.