A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.

How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly available datasets with our newly generated data reveal that SMARCD3 (also known as BAF60C) regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. We further identify that a core set of transcription factors, enhancer of zeste homologue 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the cis-regulatory elements at the SMARCD3 locus to form a chromatin hub to control SMARCD3 expression in the developing cerebellum and in metastatic MB. Increased SMARCD3 expression activates Reelin-DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for patients with MB.

CircPOSTN competes with KIF1B for miR-185-5p binding sites to promote the tumorigenesis of glioma.

BACKGROUND: The involvement of certain circular RNAs (circRNAs) in the development of glioma has been revealed. CircRNA periostin (circPOSTN) was validated to be positively associated with glioma cell growth and metastasis. However, the mechanism underlying circPOSTN in glioma tumorigenesis remain vague. METHODS: The expression of circPOSTN, KIF1B (Kinesin Family Member 1B) and miR-185-5p was detected using quantitative real-time polymerase chain reaction and Western blot. In vitro assays were conducted using cell counting kit-8 assay, colony formation assay, EdU assay, flow cytometry, Western blot, and transwell assay, respectively. The direct interactions between miR-185-5p and circPOSTN or KIF1B was confirmed by using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: CircPOSTN was highly expressed in glioma tissues and cells. Knockdown of circPOSTN restrained glioma cell proliferation, migration and invasion in vitro, as well as hindered glioma xenograft growth in vivo. Mechanistically, circPOSTN acted as miR-185-5p sponge to up-regulate the expression of its target KIF1B. Moreover, miR-185-5p inhibition reversed the anticancer effects of circPOSTN knockdown on glioma tumorigenesis, and miR-185-5p re-expression suppressed the malignant phenotype of glioma cells via targeting KIF1B. CONCLUSION: CircPOSTN acted as an oncogene to expedite glioma tumorigenesis via targeting miR-185-5p/KIF1B axis, indicating a potential therapeutic target for glioma.

Cerebral cysticercosis mimicking subarachnoid hemorrhage: a case report.

BACKGROUND: Dense exudate during the calcification of cerebral cysticercosis in basal subarachnoid space was easy to be misdiagnosed as subarachnoid hemorrhage (SAH); clinical evaluation and MRI can help differentiate SAH from pseudo-SAH. CASE PRESENTATION: A case of ventricular expansion accompanied by high-density shadows in cisterna circinata cerebri was taken to the hospital for treatment due to sudden faint. This patient was diagnosed as subarachnoid hemorrhage according to computed tomography (CT) in another hospital. We believe that the high density in cisterna circinata cerebri was misdiagnosed as subarachnoid hemorrhage (SAH) 1 year ago. The main etiology of SAH is aneurysm; non-aneurysmal SAH associated with cerebral cysticercosis is extremely rare. Only 5 patients have been reported. CONCLUSION: This case indicated that although the specificity of CT for SAH is very high, the physicians should be aware of rare false positive findings, called pseudo-SAH.

Circular RNA circPITX1 knockdown inhibits glycolysis to enhance radiosensitivity of glioma cells by miR-329-3p/NEK2 axis.

BACKGROUND: Numerous circular RNAs (circRNAs) have been recognized as vital modulators of human malignancies, including glioma. Whereas, the functional role of circRNA Pituitary Homeo Box 1 (circPITX1) in the radioresistance of glioma cells remains largely uncertain. METHODS: Quantitative real-time PCR (qRT-PCR) or western blot analysis was employed to examine the expression of circPITX1, microRNA (miR)-329-3p and NIMA-related kinase 2 (NEK2). 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used to determine cell viability. Glycolysis was assessed by commercial kits and western blot analysis. Colony formation assay was conducted to analyze cell survival and clonogenicity capacity. The relationship among circPITX1, miR-329-3p and NEK2 was confirmed via dual-luciferase reporter assay. The in vivo function of circPITX1 was evaluated by tumor xenograft assay. RESULTS: Expression of circPITX1 and NEK2 was up-regulated in glioma tissues and cells, while miR-329-3p exhibited reverse trend. CircPITX1 knockdown repressed viability, glycolysis and colony formation, but promoted radiosensitivity of glioma cells, as well as inhibited tumor growth in vivo. MiR-329-3p was a target miRNA of circPITX1 and miR-329-3p deficiency reversed knockdown of circPITX1-mediated glycolysis inhibition and radioresistance reduction. MiR-329-3p exerted inhibitory effects on glycolysis and radioresistance of glioma cells by targeting NEK2. CircPITX1 facilitated NEK2 expression by sponging miR-329-3p. Glycolytic inhibitor 2-deoxy-d-glucose (2-DG) disposition weakened the promoted impact on glycolysis caused by circPITX1. CONCLUSION: CircPITX1 knockdown reduced glycolysis to contribute to radiosensitivity in glioma through miR-329-3p/NEK2 axis, providing a possible mechanism of circPITX1 in the development of glioma.

Gremlin1 promotes carcinogenesis of glioma in vitro.

As the most prevalent and lethal type of brain tumours, gliomas, especially malignant ones, are relatively resistant to conventional therapies. Gremlin 1 (GREM1) is a secreted glycoprotein that is implicated in the maintenance of cancer stem cells in tumour hierarchy. In the current study, the role of GREM1 in the carcinogenesis of glioma was studied using a knockdown approach. We first examined the expression level of GREM1 in the clinical samples, and then evaluated the effect of GREM1 knockdown on the viability and colony formation capacity of U87-MG cells. Moreover, the migration ability, invasiveness, cell cycle, and apoptosis of GREM1-silenced cells were assessed. Furthermore, the involvement of functional GREM1 in the epithelial-mesenchymal transition (EMT) process of glioma was investigated by detecting the expression levels of glioma-associated oncogene homologue 3 (GLI3) and EMT-related molecules. Our results demonstrated that knockdown of GREM1 reduced cell viability, suppressed migration and invasion, and inhibited GLI3 expression and the EMT process in U87-MG cells. Meanwhile, GREM1 silencing promoted apoptosis in U87-MG cells through the accumulation of Bax, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) as well as the downregulation of Bcl-2. In addition, GREM1 knockdown abolished transforming growth factor (TGF)-ß1-mediated activation of the Smad pathway, which may underlie the mechanism of GREM1-regulated EMT. In conclusion, GREM1 plays an important role in the development of glioma, and it may serve as a potential target in glioma therapy.

Double function of noninvasive intracranial pressure monitoring based on flash visual evoked potentials in unconscious patients with traumatic brain injury.

Intracranial pressure (ICP) monitoring based on flash visual evoked potentials (F-VEP) is a noninvasive method of monitoring ICP. The early diagnosis of traumatic optic neuropathy (TON) in unconscious patients with traumatic brain injury (TBI) is a challenge. The aim of this study was to evaluate the function of F-VEP ICP monitoring in predicting TON and detecting contusion enlargement (CE) in unconscious TBI patients using a modified approach. A series of F-VEP ICP-monitored unconscious TBI patients were included in the study. The interocular differences in N2 wave latency (DL) and amplitude (DA) were obtained through monocular flash stimulation. The increases in ICP (dxP) and interchannel difference (dxDC) across various time points were obtained through binocular flash stimulation. The predictive power of DL and DA on TON, as well as of dxP and dxDC on CE, was assessed by logistic regression and receiver operating characteristic (ROC) curve analysis. Patients with TON had a longer DL and a higher DA than those without TON. The dxP and dxDC of patients with CE were both higher than those of patients without CE. The differences were statistically significant. The logistic regression showed that both DL and DA were predictors of TON, whereas only dxDC was a predictor of CE. However, the ROC curve analysis showed that DL had greater predictive power for TON, and dxDC had greater predictive power for CE. An F-VEP ICP monitoring system with a modified approach is beneficial for early diagnosis of TON and prediction of CE in unconscious TBI patients.

Factors affecting the evacuation rate of intracerebral hemorrhage in basal ganglia treated by minimally invasive craniopuncture.

OBJECTIVE: Minimally invasive craniopuncture has been used to treat intracerebral hemorrhage (ICH) for over 20 years in China. However, one-off total evacuation of hematoma cannot be achieved through this procedure because it is not an open surgery. This study is designed to identify factors that can increase the hematoma evacuation rate (ER) of this procedure and to evaluate the influence of ER on long-term outcome. METHODS: A total of 309 patients with basal ganglia ICH treated by minimally invasive craniopuncture were analyzed retrospectively. Univariate and multivariate linear regression analyses were used to identify factors correlated with a high ER. The correlation between ER and long-term outcome was also analyzed by logistic regression and the Spearman correlation. RESULTS: A low hematoma mean CT number (ß=-0.773, p<0.001) and postoperative cerebrospinal fluid (CSF) outflow (ß=0.193, p<0.001) were found to be independent factors associated with a high ER. In patients with 30-50ml of hematoma, a high ER was correlated with a high Barthel index improvement (r=0.611, p<0.001) and a high modified Rankin scale decline (r=0.517, p<0.001). In patients with 50-80ml of hematoma, a high ER was a protective factor of case fatality (B=-2.297, p=0.005). CONCLUSIONS: The hematoma mean CT number can predict the efficiency of minimally invasive craniopuncture in patients with ICH. In patients with ventricular involvement, the tip of the puncture needle should be placed close to the tear in the ventricle rather than at the center of the hematoma to facilitate postoperative CSF outflow.