Tranrooney2167

Background The chromatin insulator CCCTC-binding factor (CTCF) displays tissue-specific DNA binding sites that regulate transcription and chromatin organization. Despite evidence linking CTCF to the protection of epigenetic states through barrier insulation, the impact of CTCF loss on genome-wide DNA methylation sites in human cancer remains undefined. Results Here, we demonstrate that prostate and breast cancers within The Cancer Genome Atlas (TCGA) exhibit frequent copy number loss of CTCF and that this loss is associated with increased DNA methylation events that occur preferentially at CTCF binding sites. CTCF sites differ among tumor types and result in tissue-specific methylation patterns with little overlap between breast and prostate cancers. DNA methylation and transcriptome profiling in vitro establish that forced downregulation of CTCF leads to spatially distinct DNA hypermethylation surrounding CTCF binding sites, loss of CTCF binding, and decreased gene expression that is also seen in human tumors. DNA methylation inhibition reverses loss of expression at these CTCF-regulated genes. Conclusion These findings establish CTCF loss as a major mediator in directing localized DNA hypermethylation events in a tissue-specific fashion and further support its role as a driver of the cancer phenotype.Background Apoptosis is fundamental in maintaining cell balance in multicellular organisms, and caspases play a crucial role in apoptosis pathways. It is reported that apoptosis plays an important role in tick salivary gland degeneration. Several different caspases have been found in ticks, but the interactions between them are currently unknown. Here, we report three new caspases, isolated from the salivary glands of the tick Rhipicephalus haemaphysaloides. Methods The full-length cDNA of the RhCaspases 7, 8 and 9 genes were obtained by transcriptome, and RhCaspases 7, 8 and 9 were expressed in E. coli; after protein purification and immunization in mice, specific polyclonal antibodies (PcAb) were created in response to the recombinant protein. Reverse-transcription quantitative PCR (RT-qPCR) and western blot were used to detect the existence of RhCaspases 7, 8 and 9 in ticks. TUNEL assays were used to determine the apoptosis level in salivary glands at different feeding times after gene silencing. The interd 9 expressions. NK012 Co-transfection assays showed RhCaspase7 was cleaved by RhCaspases 8 and 9, demonstrating that RhCaspases 8 and 9 are initiator caspases and RhCaspase7 is an executioner caspase. Conclusions To the best of our knowledge, this is the first study to identify initiator and executioner caspases in ticks, confirm the interaction among them, and associate caspase activation with tick salivary gland degeneration.Background Recent studies have indicated that a ketogenic diet can be used as an adjuvant therapy to enhance sensitivity to chemotherapy and radiotherapy in cancer patients. However, there are no sufficient data and no consistent international treatment guidelines supporting a ketogenic diet as an adjuvant therapy for metastatic breast cancer. Therefore, this trial was designed to observe whether irinotecan with a ketogenic diet can promote sensitivity to chemotherapy and remit target lesions in locally recurrent or metastatic Her-2-negative breast cancer patients. Methods/design This trial aims to recruit 518 women with locally recurrent or metastatic breast cancer admitted to the Liaoning Cancer Hospital and Institute (Shenyang, China) in northeast China. All patients will be randomly assigned into the combined intervention group (n = 259) or the control group (n = 259), followed by treatment with irinotecan + ketogenic diet or irinotecan + normal diet, respectively. The primary endpoints are sensitivity to irinotecan and the objective response rate of target lesions; the secondary endpoints include quality of life scores (EORTC QLQ-C30), progression-free survival, overall survival time, incidence of adverse events, and cost-effectiveness. The endpoints will be evaluated at baseline (before drug administration), during treatment, 4 weeks after treatment completion, and every 3months (beginning 2 months after treatment completion). Discussion This trial attempts to investigate whether irinotecan treatment with a ketogenic diet for locally recurrent or metastatic breast cancer among women in northeast China can enhance the disease's sensitivity to chemotherapy and reduce target lesions. Trial registration Chinese Clinical Trial Registry, ID ChiCTR1900024597. Registered on 18 July 2019. Protocol Version 1.1, 24 February 2017.Background Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis. Methods RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607. Results In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promoted apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulated Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic. Conclusion The results of the present study revealed that circ_0078607 suppressed ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.