Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1a) at the posttranscriptional level. HIF1a bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression.Significance: These findings suggest that inhibition of Linc01060containing exosomes or targeting the Linc01060/MZF1/c-Myc/ HIF1a axis may be an effective therapeutic strategy in glioma.
The upregulation of ELTD1 ([epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing 1] on chromosome 1) in tumor cells has been reported in several types of cancer and correlates with poor cancer prognosis. However, the role of ELTD1 in glioma progression remains unknown. In this study, we examined ELTD1 expression levels in human glioma cell lines and in sixteen human gliomas of different grades. The molecular effects of ELTD1 in glioma cells were measured using quantitative polymerase chain reaction (qRT-PCR), Western blotting, Cell proliferation assays, Matrigel migration and invasion assays and brain orthotopic xenografts. We found that high expression levels of ELTD1 were positively associated with cancer progression and poor prognosis in human glioma. Mechanistically, ELTD1 activated the JAK/STAT3/HIF-1α signaling axis and p-STAT3 bound with HIF-1α. Taken together, our data provide a plausible mechanism for ELTD1-modulated glioma progression and suggest that ELTD1 may represent a potential therapeutic target in the prevention and therapy of glioma.
A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD.
Our outcomes demonstrated the Arantius ligament suspension technique is a feasible and ideal method during laparoscopic isolated caudate lobectomy for providing a rapid and safe left lateral lobe retraction.
Background Cumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC). Methods 468 consecutive ICC patients who underwent hepatectomy between 2010 and 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated. Results The PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG = 1: hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI 0.062–0.768) from 0.625 (95% CI 0.585–0.665) when the PRG was incorporated (p < 0.001). Conclusions The PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC.
Background Glioma is a primary malignancy of the central nervous system (CNS). As biomedicine advances, an efficient molecular target is urgently needed for the diagnosis and treatment of glioma. Meanwhile, several studies have demonstrated that glioma development is closely related to immunity. PARP9 is an inactive mono‐ADP‐ribosyltransferase belonging to the poly‐ADP ribosyltransferase (ARTD) family. In this article, we aimed to reveal the relationship between PARP9 and glioma and explore the potential prognostic value and immunotherapeutic targetability of PARP9 in glioma. Methods PARP9 transcript levels were analyzed with TCGA and GEO databases. The clinicopathological information of patients with glioma in the TCGA database and gene expression profiles were analyzed to determine the relationship between the expression of PARP9 and clinicopathologic characteristics. Kaplan‐Meier survival analysis, univariate Cox regression analysis, and multivariate Cox regression analysis were used for survival analysis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for bioinformatics analysis. Correlation analysis explored the relationships between PARP9, infiltrating inflammatory immune cells, and immune checkpoint molecules. Results PARP9 is highly expressed in glioma, and high expression of PARP9 is associated with poor prognosis and advanced clinicopathological features. Bioinformatics analysis showed that some immune‐related pathways were closely associated with high expression of PARP9. Correlation analysis indicated that PARP9 was closely related to inflammatory and immune responses, high immune cell infiltration, and immune checkpoint molecules. Conclusions PARP9 may serve as an unfavorable prognosis predictor for glioma and a potential immunotherapeutic target.
The blood-brain barrier (BBB) is an essential structure of the central nervous system (CNS), and its existence makes the local internal environment of the CNS a relatively independent structure distinct from other internal environments of the human body to ensure normal physiological and high stability of activities of the CNS. Changes in BBB structure and function are fundamental to the pathophysiology of many diseases. The occurrence and development of glioma are often accompanied by a series of changes in the structure and function of the internal environment, the most significant of which is remodelling of the BBB. The remodelling of the BBB usually leads to changes in the permeability of local microvessels, which provide certain favourable conditions for the occurrence and development of glioma. Meanwhile, the newly generated abnormal blood vessels and the remaining intact regions of the BBB also hinder the effects of drug treatments. Changes in permeability and structural function often lead to the creation of abnormally functioning vascular regions, which pose further treatment challenges. At present, therapeutic methods for glioma have not achieved satisfactory effects in clinical practice, and emerging therapeutic methods have not yet been widely used in clinical practice. In this review, we summarize the knowledge of remodelling of the BBB in the glioma environment, the type of changes that occur, and current BBB treatment methods and prospects for the treatment of glioma.
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