RESUMO
The infection and colonization of pathogenic fungi are often regulated by transcription factors. In our previous study, the zinc finger protein-encoding gene StMR1 was found to be highly expressed during the infection process of Setosphaeria turcica, the pathogen causing northern corn leaf blight. Evolutionary tree analysis showed that this gene was associated with regulatory factors of melanin synthesis. However, the regulatory mechanism of melanin synthesis and its effect on pathogenicity remain unclear. In this study, the function of StMR1 was analyzed by gene knockout. When the expression level of StMR1 in the mutants was significantly reduced, the colony color became lighter, the mycelia were curved and transparent, and the mutant showed a significant loss of pathogenicity. In addition, compared with wild-type, the accumulation of melanin decreased significantly in ΔStmr1. RNA-seq analysis revealed 1,981 differentially expressed genes between the wild-type and knockout mutant, among which 39 genes were involved in melanin metabolism. qPCR revealed that the expression levels of six key genes in the melanin synthesis pathway were significantly reduced. ChIP-PCR and yeast one-hybrid assays confirmed that StMR1 directly binds to the promoters of St3HNR, St4HNR, StPKS, and StLAC2 in the DHN melanin synthesis pathway and regulates gene expression. The C2H2-type zinc fingers and Zn(â ¡)2Cys6 binuclear cluster in StMR1 were important for the binding to targets.
Assuntos
Melaninas , Doenças das Plantas , Ascomicetos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Doenças das Plantas/microbiologia , Virulência , Dedos de ZincoRESUMO
BACKGROUND: Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV. Ubiquitin-conjugating enzyme E2S (UBE2S), a potential oncogene, regulates the malignant progression of various tumors; however, its role in OV is still unclear. METHODS: The expression and prognostic significance of UBE2S at the pan-cancer level were investigated through high-throughput gene expression analysis and clinical prognostic data from TCGA, GEPIA, and GEO databases. 181 patients with OV were included in this study. Cell culture and cell transfection were performed on OV cell lines (SKOV3 and A2780) and a normal ovarian cell line (IOSE80). The expression level and prognostic significance of UBE2S in OV were verified by western blot, immunohistochemistry, and Kaplan-Meier survival analysis. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, Transwell, clonogenic, and flow cytometry assays, the effect and detailed mechanism of UBE2S knockdown on the malignant biological behavior of OV cells were explored. RESULTS: UBE2S exhibited abnormally high expression at the pan-cancer level. The results of RT-qPCR and Western blotting indicated that UBE2S was significantly overexpressed in ovarian cancer cell lines compared with normal cell lines (P < 0.05). Kaplan-Meier survival analysis and Immunohistochemistry indicated that overexpression of UBE2S was related to poor prognosis of OV (HR > 1, P < 0.05). Results of in vitro experiments indicated that UBE2S gene knockdown might inhibit the proliferation, invasion, and prognosis of OV cells by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby blocking the cell cycle and promoting apoptosis (P < 0.05). CONCLUSION: UBE2S is a potential oncogene strongly associated with a poor prognosis of OV patients. Knockdown of UBE2S could block the cell cycle and promote apoptosis by inhibiting the PI3K/AKT/mTOR pathway and ultimately inhibit the proliferation, migration and prognosis of ovarian cancer, which suggested that UBE2S might be used for molecular therapy and prognostic evaluation of ovarian cancer.
Assuntos
Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Apoptose , Carcinoma Epitelial do Ovário/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Feminino , Humanos , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
BACKGROUND: The objective of the study is to explore the effects of retrosternal and prevertebral lifting paths of the tubular stomach on postoperative complications of patients undergoing cervical anastomosis in thoracoscopic and laparoscopic esophagectomy. METHODS: Sixty-three patients were retrospectively analyzed. The patients received thoracoscopic and laparoscopic esophagectomy by the same surgeon. According to the path by which the stomach was lifted upward, the patients were divided into two groups: the retrosternal path group (32 patients) and the prevertebral path group (31 patients). Operative indications and complications of postoperative patients in these two groups were observed. RESULTS: There was no statistically significant difference in the time duration of surgery, amount of bleeding, number of dissected lymph node, and postoperative hospitalization time between the retrosternal and prevertebral lifting paths (P > 0.05). Furthermore, the two groups did not show significant difference in the incidence rate of postoperative anastomosis fistula complications (P = 0.702). Instead, the amount of postoperative gastric drainage and the incidence rates of the pulmonary infection were significantly lower in the retrosternal path group than in the prevertebral path group, respectively (P = 0.001, P = 0.012, respectively). CONCLUSION: The esophagogastrostomic cervical anastomoses performed via the retrosternal and prevertebral paths are both feasible methods of digestive tract reconstruction. The amount of postoperative gastric drainage volume and the pulmonary infection incidence rate in the retrosternal path group were lower than those in the prevertebral path group. Therefore, gastroesophageal anastomosis via the retrosternal lifting path may be preferably considered for thoracoscopic and laparoscopic surgery for esophageal carcinoma patients.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Toracoscopia/métodos , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Feminino , Humanos , Incidência , Laparoscopia/efeitos adversos , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Prognóstico , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Estômago/cirurgia , Toracoscopia/efeitos adversosRESUMO
BACKGROUND: miR-200a-3p is involved in the progression of malignant behavior in various tumors, and its mechanism of action in endometrial cancer is speculated to be related to epithelial-mesenchymal transition (EMT). Therefore, this study explored the metastatic mechanism of miR-200a-3p and EMT in endometrial cancer, with the aim of identifying potential therapeutic targets. METHODS: qRT-PCR was used to analyze miR-200a-3p expression in HEC-1B and Ishikawa cell lines. The cell proliferation assay, transwell assay, and cell scratch test were used to assess changes in the malignant phenotypes of cells after regulating miR-200a-3p expression. Changes in EMT-related protein zinc finger E-box binding homeobox 1 (ZEB1) were detected after regulating miR-200a-3p expression. An endometrial carcinoma transplantation mouse tumor model was constructed, and multiple EMT-related proteins were examined. RESULTS: The expression of miR-200a-3p and ZEB1 in the endometrial cancer cell lines was higher than in normal endometrial epithelial cell lines (P < 0.05). After silencing miR-200a-3p, the expression of EMT-related protein ZEB1 increased, indicating a negative correlation. Simultaneously, the proliferation, invasion, and metastasis of endometrial cancer cells were significantly enhanced. After miR-200a-3p overexpression, the corresponding malignant phenotype was reversed (P < 0.05). In in vivo experiments, the degree of tumor malignancy and the expression level of EMT-related proteins were significantly reduced in the miR-200a-3p mimic group (P < 0.05). CONCLUSION: This study found that miR-200a-3p is a promising target, regulating the EMT process and promoting endometrial cancer progression.
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Background: Endometrial cancer is one of the three major gynecologic malignancies, and its incidence continues to rise. ATPase family AAA structural domain-containing protein 2 (ATAD2) is an ATPase protein, which is an independent factor for poor prognosis in endometrial cancer. However, its role in the disease is yet to be determined. Methods: The Tumor IMmune Estimation Resource (TIMER) database was used to assess ATAD2 expression in pan-cancer, and the relevance of ATAD2 expression in Uterine Corpus Endometrial Carcinoma (UCEC) in clinical settings was obtained using Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN analysis. In addition, the Human Protein Atlas database was used to assess ATAD2 protein expression in UCEC. Furthermore, in vitro molecular biology and in vivo functional experiments were employed to ascertain the effect of ATAD2 expression on tumor angiogenesis and tumor growth. UALCAN was used to screen for ATAD2 coexpressed genes, and Sangerbox was utilized to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these coexpressed genes. Finally, the TIMER, Tumor Immune System Interaction and Drug Bank (TISIDB), and GEPIA databases were used to analyze the relationship between ATAD2 and immune infiltration. Results: ATAD2 is highly expressed in a variety of tumors, and in UCEC, it plays the role of a protooncogene. Basic experiments revealed that ATAD2 promotes vascular endothelial growth factor expression in endometrial cancer and affects tumor growth and angiogenesis. In addition, GO and KEGG enrichment analyses showed that ATAD2-associated genes were chiefly enriched in certain signaling pathways, such as herpes simplex virus 1 infection and that ATAD2 was associated with immune infiltration in UCEC. Conclusion: Our findings suggest that ATAD2 promotes tumor growth and angiogenesis in endometrial cancer. Furthermore, ATAD2 is associated with immune infiltration and is a potential diagnostic and therapeutic target.
Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Feminino , Humanos , Fator A de Crescimento do Endotélio Vascular , Neoplasias do Endométrio/genética , Regulação para Cima , Adenosina Trifosfatases/genética , ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas de Ligação a DNA/genéticaRESUMO
The present study was carried out to elucidate the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The levels of sixteen amino acids and amines in microdialysate were monitored by capillary electrophoresis analysis. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results demonstrate that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter gamma-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusion. This study provides the first in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by modulating the release of multiple neurotransmitters and neuromodulators during ischemia/reperfusion.