RESUMEN
The study investigated the potential association of the low-density lipoprotein (LDL) genome with endometrial cancer progression based on the Gene Expression Omnibus data set and The Cancer Genome Atlas data set. Differential and weighted gene coexpression network analysis was performed on endometrial cancer transcriptome datasets GSE9750 and GSE106191. The protein-protein interaction network was built using LDL-receptor proteins and the top 50 tumor-associated genes. Low-density lipoprotein-related receptors 5/6 (LRP5/6) in endometrial cancer tissues were correlated with oncogenes, cell cycle-related genes, and immunological checkpoints using Spearman correlation. MethPrimer predicted the LRP5/6 promoter CpG island. LRP2, LRP6, LRP8, LRP12, low-density lipoprotein receptor-related protein-associated protein, and LRP5 were major LDL-receptor-related genes associated with endometrial cancer. LRP5/6 was enriched in various cancer-related pathways and may be a key LDL-receptor-related gene in cancer progression. LRP5/6 may be involved in the proliferation process of endometrial cancer cells by promoting the expression of cell cycle-related genes. LRP5/6 may be involved in the proliferation of endometrial cancer cells by promoting the expression of cell cycle-related genes. LRP5/6 may promote the immune escape of cancer cells by promoting the expression of immune checkpoints, promoting endometrial cancer progression. The MethPrimer database predicted that the LRP5/6 promoter region contained many CpG islands, suggesting that DNA methylation can occur in the LRP5/6 promoter region. LRP5/6 may aggravate endometrial cancer by activating the phosphoinositide 3-kinase/protein kinase B pathway.
Asunto(s)
Neoplasias Endometriales , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Humanos , Femenino , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Fosfatidilinositol 3-Quinasas , Receptores de LDL , Neoplasias Endometriales/genética , Lipoproteínas LDLRESUMEN
BACKGROUND: The role of Feline sarcoma-related protein (Fer) in various cancers has been extensively studied, but its specific involvement and underlying mechanisms in the progression of endometrial carcinoma (EC) are yet to be fully understood. METHODS: The expression levels of Fer were assessed in EC tissues and cell lines using real-time quantitative PCR and western blot analysis. CCK-8 assay, Edu staining, transwell assays, and flow cytometry, were conducted to evaluate the impact of Fer on EC cells. Furthermore, a mice xenograft model and immunohistochemistry (IHC) staining were utilized for in vivo analysis. The levels of Ras, pMek1/2, and pErk1/2 were determined by western blot assay. Ras-MAPK signaling pathway inhibitor was utilized to study the regulatory role of Fer on EC cells. RESULTS: Our findings revealed that Fer exhibited upregulation in both EC tissues and cell lines, concomitant with the activation of the Ras-MAPK signaling pathway. Silencing of Fer resulted in the suppression of cell proliferation, migration, invasion, and Ras-MAPK signaling pathway, while promoted hypoxia-induced apoptosis in RL95-2 and KLE cells. Fer overexpression stimulated cell proliferation, migration, invasion, and Ras-MAPK signaling pathway in Ishikawa and AN3-CA cells, which were reversed after treatment with either Ras or MAPK inhibitor. Moreover, silencing of Fer suppressed tumor growth and downregulated the expression of Ki-67, Ras, pMek1/2, and pErk1/2, but had no significant effect on Mek1/2 and Erk1/2, while upregulated caspase-3 expression in vivo. CONCLUSION: In summary, the upregulation of Fer in EC cells resulted in the enhancement of cell proliferation, migration, and invasion through the activation of the Ras-MAPK signaling pathway.
RESUMEN
Vegetative storage proteins (VSPs) are known to serve as nitrogen reserves in many dicot plants but remain undiscovered in grasses, most widely grown group of crops globally. We identified and characterized a VSP in maize and demonstrated that its overexpression improved drought tolerance. Nitrogen supplementation selectively induced a mesophyll lipoxygenase (ZmLOX6), which was targeted to chloroplasts by a novel N-terminal transit peptide of 62 amino acids. When ectopically expressed under the control of various tissue-specific promoters, it accumulated to a fivefold higher level upon expression in the mesophyll cells than the wild-type plants. Constitutive expression or targeted expression specifically to the bundle sheath cells increased its accumulation by less than twofold. The overexpressed ZmLOX6 was remobilized from the leaves like other major proteins during grain development. Evaluated in the field over locations and years, transgenic hybrids overexpressing ZmLOX6 in the mesophyll cells significantly outyielded nontransgenic sibs under managed drought stress imposed at flowering. Additional storage of nitrogen as a VSP in maize leaves ameliorated the effect of drought on grain yield.
Asunto(s)
Sequías , Zea mays , Cloroplastos , Grano Comestible/genética , Nitrógeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Zea mays/genéticaRESUMEN
The coleopteran insect western corn rootworm (WCR, Diabrotica virgifera virgifera) is an economically important pest in North America and Europe. Transgenic corn plants producing Bacillus thuringiensis (Bt) insecticidal proteins have been useful against this devastating pest, but evolution of resistance has reduced their efficacy. Here, we report the discovery of a novel insecticidal protein, PIP-47Aa, from an isolate of Pseudomonas mosselii. PIP-47Aa sequence shows no shared motifs, domains or signatures with other known proteins. Recombinant PIP-47Aa kills WCR, two other corn rootworm pests (Diabrotica barberi and Diabrotica undecimpunctata howardi) and two other beetle species (Diabrotica speciosa and Phyllotreta cruciferae), but it was not toxic to the spotted lady beetle (Coleomegilla maculata) or seven species of Lepidoptera and Hemiptera. Transgenic corn plants expressing PIP-47Aa show significant protection from root damage by WCR. PIP-47Aa kills a WCR strain resistant to mCry3A and does not share rootworm midgut binding sites with mCry3A or AfIP-1A/1B from Alcaligenes that acts like Cry34Ab1/Cry35Ab1. Our results indicate that PIP-47Aa is a novel insecticidal protein for controlling the corn rootworm pests.
Asunto(s)
Bacillus thuringiensis/metabolismo , Zea mays/metabolismo , Zea mays/microbiología , Animales , Control Biológico de Vectores , Plantas Modificadas Genéticamente/metabolismo , Plantas Modificadas Genéticamente/microbiologíaRESUMEN
OBJECTIVE: The aim of this study was to compare the characteristics of two orthotopic xenograft models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3. MATERIALS AND METHODS: Tumor tissues and cell line OVCAR3 of human epithelial ovarian cancer were grown in subcutaneous tissue and the subcutaneous tumor source was fetched and inoculated in ovarian capsule of nude mice under microscope to establish the orthotopic implantation model. At four and eight weeks after modeling, the orthotopic tumor formation rate, tumor diameter, metastasis rate outside the ovary, incidence rate of ascites, and CA125 levels in the two models were observed. RESULTS: The orthotopic tumor formation rate in the solid tumor slices group (60.0%) was significantly lower than that in the cell line group (85.0%, p < 0.05). However, the tumor diameter, metastasis rate outside the ovary, incidence rate of ascites, and CA125 levels in the solid tumor slices group (2.4 +/- 0.61 cm, 75.0%, 50.0%, and 80.13 +/- 11.26 U/ml, respectively) were remarkably higher than those in the cell line group (1.6 +/- 0.53 cm, 52.9%, 29.4%, and 36.5 +/- 6.71 U/ml, respectively) (p < 0.05, respectively). CONCLUSION: There are differences between the two orthotopic xenograft models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3. The biological characteristics of the solid tumor slices model are more similar to human ovarian cancer.
Asunto(s)
Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Animales , Antígeno Ca-125/sangre , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Femenino , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
BACKGROUND: Endometrial cancer is a malignant tumour with a high incidence and mortality rate, and obesity is one of the most significant risk factors for the disease. However, it remains unclear whether leptin affects cell activity, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: Samples of endometrial cancer tissue were obtained from clinical patients and nude mice Enzyme-linked immunosorbent assays (ELISAs) were performed to assess leptin levels. Western blotting, immunohistochemical (IHC) and immunofluorescence (IF) analyses were conducted to detect EMT, JAK2/STAT3 signalling pathway proteins, and cell proliferation biomarkers. Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays were used to evaluate cell activity, proliferation, migration, and invasion, respectively. RESULTS: ELISA, western blot and immunohistochemistry (IHC) analyses showed that leptin was highly expressed, and the JAK2/STAT3 signalling pathway was activated in endometrial cancer patients. Cell-based experiments showed that adipocytes secreted leptin, which increased the levels of leptin, and also promoted cell migration and invasion, EMT transition, and cell activity and proliferation. Leptin accelerated cell progression and promoted EMT via the JAK2/STAT3 signalling pathway in a dose-dependent manner. The tumour-promoting effect of leptin on endometrial cancer cells was further verified by in vivo experiments, in which leptin promoted tumour growth and activated the JAK2/STAT3 signalling pathway. CONCLUSION: Leptin secreted by adipocytes promotes EMT transition and endometrial cancer progression via the JAK2/STAT3 signalling pathway in a dose-dependent manner.Highlights Endometrial cancer patients have high levels of leptinLeptin promotes EMT transition via the JAK2/STAT3 signalling pathwayLeptin promotes endometrial cancer progression via the JAK2/STAT3 signalling pathwayLeptin promotes endometrial cancer in a dose-dependent manner.
Asunto(s)
Neoplasias Endometriales , Leptina , Animales , Femenino , Humanos , Ratones , Adipocitos/metabolismo , Línea Celular Tumoral , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Transición Epitelial-Mesenquimal , Janus Quinasa 2/metabolismo , Leptina/metabolismo , Ratones Desnudos , Factor de Transcripción STAT3/metabolismoRESUMEN
Cisplatin-based chemotherapy is the standard treatment for metastatic ovarian cancer (OC). However, chemoresistance continues to pose significant clinical challenges. Recent research has highlighted the baculoviral inhibitor of the apoptosis protein repeat-containing 5 (BIRC5) as a member of the inhibitor of the apoptosis protein (IAP) family. Notably, BIRC5, which has robust anti-apoptotic capabilities, is overexpressed in numerous cancers. Its dysfunction has been linked to challenges in cancer treatment. Yet, the role of BIRC5 in the chemoresistance of OC remains elusive. In our present study, we observed an upregulation of BIRC5 in cisplatin-resistant cell lines. This upregulation was associated with enhanced chemoresistance, which was diminished when the expression of BIRC5 was silenced. Intriguingly, BIRC5 exhibited a high number of N6-methyladenosine (m6A) binding sites. The modification of m6A was found to enhance the expression of BIRC5 by recognizing and binding to the 3'-UTR of mRNA. Additionally, the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was shown to stabilize BIRC5 mRNA, synergizing with METTL3 and intensifying chemoresistance. Supporting these in vitro findings, our in vivo experiments revealed that tumors were significantly smaller in size and volume when BIRC5 was silenced. This reduction was notably counteracted by co-silencing BIRC5 and overexpressing IGF2BP1. Our results underscored the pivotal role of BIRC5 in chemoresistance. The regulation of its expression and the stability of its mRNA were influenced by m6A modifications involving both METTL3 and IGF2BP1. These insights presented BIRC5 as a promising potential therapeutic target for addressing cisplatin resistance in OC.
Asunto(s)
Cisplatino , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas , Proteínas de Unión al ARN , Survivin , Femenino , Cisplatino/farmacología , Cisplatino/uso terapéutico , Humanos , Resistencia a Antineoplásicos/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Survivin/metabolismo , Survivin/genética , Línea Celular Tumoral , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Animales , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Regiones no Traducidas 3' , Ratones Desnudos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Apoptosis , Adenosina/análogos & derivados , MetiltransferasasRESUMEN
BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.
Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Epigénesis Genética , China , Neoplasias de Cabeza y Cuello/genética , MutaciónRESUMEN
OBJECTIVE: To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. METHODS: The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. RESULTS: (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. CONCLUSIONS: Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.
Asunto(s)
Preservación de la Fertilidad , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Ováricas/cirugía , Ovariectomía/métodos , Adolescente , Adulto , Biopsia con Aguja , Quimioterapia Adyuvante , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/patología , Epiplón/patología , Epiplón/cirugía , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Background: Cholesterol-rich low-density lipoprotein (LDL) particles have been demonstrated to regulate breast cancer cell proliferation and migration, but their biological function and relevant mechanisms in endometrial carcinoma (EC) remain unclear. Methods: Serum and tissue samples were collected from EC patients (n = 50) and patients with benign endometrial hyperplasia (n = 50). Ishikawa and RL95-2 cells were stimulated with different concentrations of LDL, followed by treatment with a JAK2 inhibitor (SD-1029). LDL concentrations were determined by ELISA. The in vitro biological behavior of cells was examined using the CCK-8 assay, EdU staining, and Transwell assay. The tumorigenicity of LDL in vivo was examined using a xenograft mouse model. western blotting, immunofluorescence, and immunohistochemistry studies were performed to measure related protein expression. Results: The LDL concentrations and levels of p-JAK2 and p-STAT3 expression were elevated in the clinical samples. Similar trends in expression were detected in EC cells after LDL stimulation. LDL treatment significantly promoted EC cell proliferation, migration, and invasion, and also upregulated p-JAK2 and p-STAT3 expression in a dose-dependent manner. Moreover, SD-1029 dramatically blocked the LDL-mediated effects on EC cells. Intravenous injection of LDLs promoted tumor growth in the xenograft nude mice, and also increased p-JAK2, p-STAT3, and Ki-67 expression, and downregulated caspase-3 expression. Conclusions: These findings indicate that LDLs exert an oncogenic effect in EC cells by activating the JAK/STAT signaling pathway, and also suggest the JAK/STAT pathway as a possible therapeutic target for EC.
Asunto(s)
Carcinoma , Hiperplasia Endometrial , Neoplasias Endometriales , Femenino , Humanos , Animales , Ratones , Línea Celular Tumoral , Quinasas Janus/metabolismo , Quinasas Janus/farmacología , Transducción de Señal , Lipoproteínas LDL/farmacología , Ratones Desnudos , Movimiento Celular , Factores de Transcripción STAT/metabolismo , Factores de Transcripción STAT/farmacología , Factor de Transcripción STAT3/metabolismo , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Proliferación CelularRESUMEN
PURPOSE: Tumor-promotive tumor-associated macrophages (TAMs) and the CXCL16/CXCR6 axis have been reported to be correlated with the limited efficacy of chemotherapy in ovarian cancer (OC). However, the role of TAM-secreted CXCL16 and the mechanism by which it affects the cisplatin (DDP) resistance of OC cells remain elusive. METHODS: We induced human THP-1 monocytes to differentiate into macrophages. Next, SKOV3 and TOV-112D cells were co-cultured with the macrophages, followed by incubation with increasing concentrations of DDP. The effects of CXCL16, CXCR6, and WTAP on the DDP resistance of OC cells were investigated using the CCK-8 assay, colony formation assay, flow cytometry, and TUNEL staining. CXCL16 concentrations were determined by ELISA. Quantitative real-time PCR and western blotting were used to examine related markers. RESULTS: Our results showed that after being co-cultured with TAMs, the DDP resistance of OC cells was significantly enhanced and their CXCL16 levels were elevated. Acquired DDP resistance was characterized by an increased IC50 value for DDP, the formation of cell colonies, and decreased levels of cell apoptosis, which were accompanied by reduced levels of caspase-3 and Bax expression, and increased levels of Bcl-2, PARP1, BRCA1, and BRCA2 expression. Either CXCL16 knockdown in TAMs or CXCR6 knockdown in OC cells suppressed the DDP resistance of OC cells that had been co-cultured with TAMs. Knockdown of CXCL16 affected m6A RNA methylation in OC cells, as reflected by decreased YTHDF1/WTAP expression and increased ALKBH5 expression. WTAP overexpression and knockdown promoted and suppressed the DDP resistance of OC cells, respectively. CONCLUSION: Tumor-associated macrophages promote the cisplatin resistance of OC cells by enhancing WTAP-mediated N6-methyladenosine RNA methylation via the CXCL16/CXCR6 axis.
Asunto(s)
Cisplatino , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Macrófagos Asociados a Tumores , Metilación , Neoplasias Ováricas/tratamiento farmacológico , ARN/farmacología , ARN/uso terapéutico , Resistencia a Antineoplásicos , Línea Celular Tumoral , Proliferación Celular , Receptores CXCR6 , Factores de Empalme de ARN , Proteínas de Ciclo CelularRESUMEN
Hangzhou Bay is facing severe anthropogenic perturbation because of its geographic position. We studied species-specific bioaccumulation of metals in commercially important fishes and shellfishes, and calculated the potential human health hazards through their consumption, which has not been reported earlier from this area. The hierarchy of metal concentration in organisms was in the decreasing order of Zn (10.32 ± 7.13) > Cu (2.40 ± 2.66) > As (0.42 ± 0.26) > Cr (0.11 ± 0.08) > Cd (0.07 ± 0.07) > Pb (0.05 ± 0.02) > Hg (0.012 ± 0.009). Except for Cd and As concentrations in fishes, metal concentrations have not exceeded the national and international guideline values. P. laevis and P. trituberculatus were the most bioaccumulative of the species studied. According to the non-carcinogenic risk assessment, children were more susceptible to metal contamination than adults. The carcinogenic risk (CR) values indicated that children were likely to experience carcinogenic threats for taking cancer-causing agents As and Cd through fish consumption. In terms of organisms, intake of two crab species, P. trituberculatus and E. sinensis, as well as the oyster species P. laevis, could be detrimental to consumers.
Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Animales , Bahías , Bioacumulación , Cadmio , China , Monitoreo del Ambiente , Peces , Humanos , Metales Pesados/análisis , Metales Pesados/toxicidad , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) participates in the development of diverse cancers. Nevertheless, the impact of DANCR on cervical cancer (CC) remains largely unknown. This study aims to explore the effects of DANCR sponging microRNA-145-3p (miR-145-3p) on CC. Expression of KLF5, DANCR, miR-145-3p, and zinc finger E-box binding homeobox 1 (ZEB1) in CC and adjacent normal tissues was determined. Human CC cell lines were, respectively, treated with silenced DANCR or miR145-3p mimic/inhibitor. Then, the viability, migration, invasion, and apoptosis of CC cells were measured. The cell growth in vivo was observed as well. Chromatin immunoprecipitation assay was performed to analyze the binding of KLF5 and DANCR promoter. Interaction among DANCR, miR-145-3p, and ZEB1 was assessed. KLF5, DANCR, and ZEB1 were upregulated but miR-145-3p was downregulated in CC tissues. KLF5 activated DANCR expression and the high DANCR expression was related to tumor staging, infiltrating muscle depth and lymphatic metastasis of CC patients. Reduced DANCR or elevated miR-145-3p repressed malignant behaviors of CC cells. The tumor diameter and weight were also repressed by DANCR silencing or miR-145-3p elevation. The effect of DANCR knockdown on CC cells could be reversed by miR-145-3p inhibitor. MiR-145-3p was targeted by DANCR and ZEB1 was targeted by miR-145-3p. KLF5-induced overexpression of DANCR promotes CC progression via suppressing miR-145-3p to target ZEB1. This study may provide potential targets for CC treatment.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. METHODS: Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. RESULTS: Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. CONCLUSION: This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.
Asunto(s)
Carcinoma Epitelial de Ovario/genética , Neoplasias de Células Germinales y Embrionarias/genética , Células Madre Neoplásicas/metabolismo , Neoplasias Ováricas/genética , ARN Circular/genética , Proteínas de Unión al ARN/genética , Animales , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Trasplante de Neoplasias , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Circular/metabolismo , Receptor ErbB-4/genética , Receptor ErbB-4/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: We analyzed TCGA dataset and observed the downregulation of CTBP1-AS2 in ovarian cancer (OC), while the function of CTBP1-AS2 has only been investigated in diabetes and cardiomyocyte hypertrophy, but not in cancer biology. We therefore analyzed the involvement of CTBP1-AS2 in OC. RESULT: We found that CTBP1-AS2 was downregulated in OC and predicted poor survival. CTBP1-AS2 in luciferase activity assay interacted with miR-216a, while overexpression of CTBP1-AS2 and miR-216a had no significant effects on the expression of each other. However, increased expression level of PTEN, a target of miR-216a, was observed after CTBP1-AS2 overexpression. Increased proliferation rate of OC cells was observed after the overexpression of miR-216a. CTBP1-AS2 and PTEN overexpression resulted in the reduced proliferation rate of OC cells and reduced effects of miR-216a overexpression. CONCLUSION: CTBP1-AS2 regulates miR-216a/PTEN to suppress OC cell proliferation.
Asunto(s)
Oxidorreductasas de Alcohol/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , MicroARNs/genética , Neoplasias Ováricas/genética , Fosfohidrolasa PTEN/genética , ARN Largo no Codificante/genética , Línea Celular Tumoral , Regulación hacia Abajo/genética , Femenino , Humanos , Neoplasias Ováricas/patología , Transducción de Señal/genéticaRESUMEN
Anthropogenic pollution has become a major issue governing ecosystem and human health risks. The Hangzhou Bay and Qiantang Estuary region are facing unusual perturbation due to rapid development along the embayment in recent decades. This study evaluated the organic and inorganic pollutants in water, sediment, and from the muscles of higher trophic organisms (fish, crustacean, shellfish) during four different seasons (in 2018-2019) along the Qiantang Estuary and Hangzhou Bay region to assess the ecosystem health and potential hazard status. Dissolved inorganic phosphate and nitrogen were the major pollutants in this area, which led to severe eutrophication throughout the study period. Eutrophication signals coincided well with the phytoplankton abundance, which revels the control of nutrient enrichment on the spatio-temporal distribution of phytoplankton. Food availability, along with salinity and temperature, drives the zooplankton population distribution. Heavy metals were not the issue of water quality as their concentrations meet the national and international baseline standards. However, in the sediments, Copper (Cu) and Arsenic (As) concentrations were higher than the baseline value. Towards the northwestern part of the Qiantang Estuary, the overall potential risk index of sediment with higher Cadmium (Cd) and Mercury (Hg) depicted delicate condition with moderate risk for the sediment contamination. The As concentration in fishes was close to the baseline standards limit irrespective of low As values within water and sediments. The higher concentrations of Zinc (Zn) and As in shellfish muscles, whereas other metals were within the limit of baseline standard in all the organisms. However, the hazard analysis (Targeted hazard quotient, THQ) values for the seafood consumption to human health indicates the potentially threatening consequences of shellfish and crustacean consumption on human health.
Asunto(s)
Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Animales , Ecosistema , Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos , Humanos , Medición de RiesgoRESUMEN
The objective of this study was to identify proteins that are differentially expressed in the cystic wall tissues of ovarian endometriotic cysts, simple ovarian cysts, and in normal ovarian tissues. Specimens of ovarian endometriotic cyst wall tissue, simple ovarian cyst wall tissue, and normal ovarian tissue (six specimens per group) were collected from patients who received gynecologic surgery, respectively. Differentially expressed proteins related to the ovarian endometriotic cysts were screened by use of isobaric tags for relative and absolute quantitation (iTRAQ) combined with functional annotation and bioinformatics analyses. All differentially expressed proteins related to cysts were validated using immunohistochemistry methods in recurrent and non-recurrent ovarian endometriotic cyst. A total of 359 proteins were identified as up-regulated in ovarian endometriotic cyst groups when compared with both the normal ovary and simple ovarian cyst groups. The levels of 27 proteins were >two-fold higher in the ovarian endometriotic cyst group than that in the other two groups. Of note, the five most significantly upregulated proteins were Charcot-Leyden Crystal Galectin (CLC), Defensin, alpha 1 (DEFA1), S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A8 (S100A8), and Ferritin Light Chain (FTL). Immunohistochemistry results showed that the changes of S100A9 and S100A8 were consistent with the results shown by iTRAQ. However, no similarity of CLC, DEFA1, and FTL proteins was found between iTRAQ and immunohistochemistry. The ratio of patients with abnormally high S100A9 and S100A8 expression in the recurrent ovarian endometriotic cyst group was significantly higher than that in the non-recurrent group (P < 0.05). Our data identify differentially expressed proteins S100A9 and S100A8, and suggest they may serve as novel molecular markers to predict postoperative recurrence of an ovarian endometriotic cysts.Abbreviations: iTRAQ: isobaric tags for relative and absolute quantitation; HPRD: Human Protein Reference Database; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; EM: Endometriosis; COX-2: cyclooxyenase-2; NF-kB: nuclear factor kappa-B; PR-B: progesterone receptor type B.
Asunto(s)
Endometriosis/metabolismo , Quistes Ováricos/metabolismo , Adulto , Biomarcadores/metabolismo , Biología Computacional , Endometriosis/complicaciones , Femenino , Perfilación de la Expresión Génica , Humanos , Quistes Ováricos/etiología , Recurrencia , Adulto JovenRESUMEN
INTRODUCTION: Estrogen receptor 1 (ESR1) plays an important role in the pathological events of ovarian cancer (OV), but the underlying mechanism is not completely understood. Using bioinformatics analysis, we found that ESR1 is involved in the regulation of some lncRNAs that are highly expressed in ovarian cancer. The lncRNAs might mediate the roles of ESR1 in OV occurrence and progression. METHODS: This study measured the expression of the lncRNAs in OV cell lines using qRT-PCR. Some of the lncRNAs were silenced or overexpressed to determine their effects on the growth and invasion of CAOV3 cells with the stimulation of 17 beta-estradiol or not. RESULTS: ESR1-expressing OV cells (CAOV3 cells) shows higher LINC00511 and RP11-166P13.3 expression than the ESR1-losing OV cells (UWB1.289 cells). Depletion of the two lncRNAs enhanced cell viability and invasion and decreased apoptosis rate. In these respects, effects of LINC00511 were more remarkable than that those of RP11-166P13.3. Treatment with 17 beta-estradiol to stimulate ESR1 increased LINC00511 expression, while ESR1 inhibitor Fulvestrant decreased LINC00511 expression. FISH assay confirmed that LINC00511 is present in the cytoplasm and nucleus. Bioinformatics analysis revealed the interaction of LINC00511 with miR-424-5p and miR-370-5p, which was further identified by RNA-pull down assay. As indicated by RIP assay, silencing LINC00511 increased the interaction between Ago protein and these two miRNAs. DISCUSSION: Our study showed that ESR1-induced upregulation of LINC00511 promoted proliferation and invasion of CAOV3 cells probably through sponging miR-424-5p and miR-370-5p.
RESUMEN
Various lepidopteran insects are responsible for major crop losses worldwide. Although crop plant varieties developed to express Bacillus thuringiensis (Bt) proteins are effective at controlling damage from key lepidopteran pests, some insect populations have evolved to be insensitive to certain Bt proteins. Here, we report the discovery of a family of homologous proteins, two of which we have designated IPD083Aa and IPD083Cb, which are from Adiantum spp. Both proteins share no known peptide domains, sequence motifs, or signatures with other proteins. Transgenic soybean or corn plants expressing either IPD083Aa or IPD083Cb, respectively, show protection from feeding damage by several key pests under field conditions. The results from comparative studies with major Bt proteins currently deployed in transgenic crops indicate that the IPD083 proteins function by binding to different target sites. These results indicate that IPD083Aa and IPD083Cb can serve as alternatives to traditional Bt-based insect control traits with potential to counter insect resistance to Bt proteins.