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Purpose To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. Materials and methods The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. Results SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. Conclusion SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.

Cancer stem cells contribute to cancer progression, but the mechanisms underlying neuroblastoma stem cell development are unclear. Here, we examined the roles of the transcription factor SLC34A2 in regulating the stemness of neuroblastoma cells. We found that SLC34A2 expression was negatively correlated with the overall survival and relapse‐free survival probability of neuroblastoma patients. Additionally, SLC34A2 expression was observed to be remarkably increased in spheroids derived from neuroblastoma cells. Knockdown of SLC34A2 attenuated the expression of stemness markers and spheroid formation capacity of neuroblastoma cell‐derived spheroids, and overexpression of SLC34A2 exerted the opposite effects in neuroblastoma cells. Mechanistically, SLC34A2 was found to directly bind to the promoter of MIR25, which targets glycogen synthesis kinase 3β (Gsk3β), an antagonist of Wnt signaling. Transfection of miR‐25 inhibitor or a Gsk3β overexpression plasmid attenuated the effects of SLC34A2 overexpression on the stemness of neuroblastoma cells. Our results demonstrate that miR‐25/Gsk3β‐mediated activation of Wnt signaling is responsible for SLC34A2‐induced enhancement of neuroblastoma cell stemness.

BackgroundGlioma is the most common malignant brain tumor in adults, with its tumor-promoting immune microenvironment always being intricate to handle with. Amounts of evidence has accumulated to suggest that alternative splicing (AS) is related to tumor immune microenvironment. However, comprehensive analysis of immune-related AS events and their clinical significance are still lacking in glioma.MethodsAS events and transcriptome data of 653 glioma patients were downloaded online. ssGSEA was performed on transcriptome data of 653 patients to divided them into low, medium and high immune cell infiltration groups. Immune-related AS events were filtrated based on this grouping. Then lasso Cox regression analysis and multivariate Cox regression analysis were done to achieve an immune-related AS events prognostic signature for glioma. Kaplan-Meier analysis, ROC analyses, univariate Cox regression and multivariate Cox regression were performed to reveal the independent prognostic role of this signature. Meanwhile, a nomogram was constructed to achieved better prognostic value for glioma patients. Besides, functional enrichment analyses and correlation analyses with immune cells infiltration were used to validated the immune-related characteristic of this signature.Results36 immune-related AS events were achieved based on the grouping mentioned above. A nine-immune-related alternative splicing event signature was built for glioma patients. This signature showed an independent prognostic value and a nomogram containing gender, age, Karnofsky performance score, grade, IDH status, MGMT promoter status and risk score derived from the signature was constructed with a higher predictive ability for overall survival. Association with the infiltration of immune cell subtypes was validated and functional enrichment analysis found that the signature was mainly enriched in immune-related and pro-tumor functions.ConclusionOur research presented all immune-related AS events in glioma, identified an immune-related prognostic AS events risk model and a nomogram was constructed to predict the prognosis individually and more precisely. Tight connection was verified between this signature and clinical characteristics. Also, immune cells infiltration and immune checkpoints expression level were proved to link to risk scores, which enhanced the understanding of relationship between AS events and glioma immune microenvironment, firstly revealing the potential role of AS in immunotherapy of glioma.

Introduction. Glioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients. Methods. In this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM. Results. Depending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups. Conclusion. The 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.

Background: Central neurocytoma is a rare intracranial tumor. Due to the limited number of reported cases, the treatment strategy for central neurocytomas, especially large central neurocytomas, remains controversial. This paper discusses our clinical experience in the treatment of large central neurocytomas.Methods: A retrospective analysis of 29 patients with intraventricular central neurocytomas diagnosed and treated by the same surgeon between April 2012 and September 2019 at the Neurosurgery Departments of Beijing Tiantan Hospital and Hainan General Hospital was performed. The clinical characteristics, treatment plans and prognoses of these patients were reviewed.Results: Among the 29 patients, the average age of onset was 31.93 (17-61) years, and the average maximum tumor diameter was 54.17 ± 15.62 mm. Twenty-three patients (79.3%) had an average maximum diameter greater than 50 mm. Twenty-seven patients (93.1%) underwent transcortical tumor resection. Twenty-seven patients (93.1%) underwent gross total tumor resection. Five patients (17.2%) received radiotherapy after the first operation, and 3 patients (10.3%) had tumor recurrence. None of the patients died.Conclusions: Surgical resection via transcortical fistulotomy is a reliable approach for removal of large central neurocytomas in the ventricle. Patients should be closely observed postoperatively, and MRI of the head should be performed regularly. If a tumor shows progression, then radiotherapy should be considered.

Background: Glioblastoma (GBM) is one of the most common primary intracranial malignancies, with limited treatment options and poor overall survival (OS). Metabolic changes in GBM have attracted wide attention in recent years, and one of the main metabolic features of cancer cells is the high level of glycolysis. Therefore, it is necessary to identify novel biomarkers associated with glycolysis in GBM. Methods: In this study, we performed gene set enrichment analysis and profiled four glycolysis-related gene sets, which revealed 327 genes associated with biological processes. Univariate and multivariate Cox regression analyses were performed to identify genes for constructing a risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI and TPBG) in the Cox proportional hazards regression model for GBM. Results: Based on this gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with better outcomes) subgroups. Multivariate Cox regression analysis showed that the prognostic power of this ten-gene signature is independent of clinical variables. Furthermore, we validated this model in two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT). In the functional analysis, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance and even an immune-suppressed microenvironment. Conclusion: The 10 glycolysis-related gene risk signature could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients.

Introduction: Pituitary adenomas constitute one of the most common intracranial tumours. The mouse double minute 2 homologue (MDM2) is considered as an important oncogene in many tumours, but it has been little studied in pituitary adenomas and the mechanism is not well understood. The purpose of this study was to investigate the function of MDM2 and its primary mechanism of action in pituitary adenoma cells. Material and methods: The expression of MDM2 in pituitary adenoma cell lines and normal cells was determined by real-time polymerase chain reaction (RT-PCR). The proliferation and apoptosis of pituitary adenoma cells after inhibition of MDM2 expression were detected by MTS and flow cytometry, respectively. The protein expressions of MDM2 and p53 were detected by western blot. Co-IP was used to detect the direct binding between MDM2 and p53. Results: The results of RT-PCR showed that MDM2 was significantly up-regulated in pituitary adenoma cell lines. Inhibition of MDM2 suppressed the proliferation and promoted apoptosis of pituitary adenoma cells. However, inhibiting the expression of MDM2 can promotethe protein expression of p53. The results of co-IP showed that MDM2 interacted with p53 by direct combination. Then, we inhibited the expressions of p53 and MDM2 simultaneously in the pituitary adenoma cells by co-transfecting siRNAs, and the results showed that, compared with the group that inhibited MDM2 alone, cell proliferation of the co-transfected group increased and apoptosis of the cotransfected group decreased, which was similar to the NC group. Conclusions: Taken together, these results suggest that MDM2 promoted the proliferation and inhibited the apoptosis of pituitary adenoma cells by directly interacting with p53 in pituitary adenoma cells. Therefore, MDM2-p53 may serve as a novel marker and therapeutic target for pituitary adenomas.

Background Central neurocytoma is a rare intracranial tumor. Due to the limited number of reported cases in the past, there is still controversy about the treatment strategy for central neurocytoma, especially large central neurocytomas occupying bilateral ventricles. This paper will discuss our clinical experience in the treatment of large central neurocytoma. Methods A retrospective analysis of 29 patients with intraventricular central neurocytoma diagnosed and treated by the same surgeon between April 2012 and September 2019 at the Neurosurgery Departments of Beijing Tiantan Hospital and Hainan General Hospital was performed. The clinical characteristics, treatment plan and prognosis of these patients were discussed. Results Among the 29 patients, the average age of onset was 31.93 (17-61) years, and the average maximum tumor diameter was 54.17 ± 15.62 mm. Among them, 23 patients (79.3%) had an average maximum diameter greater than 5 cm. Twenty-seven patients (93.1%) underwent transcortical tumor resection. Twenty-seven patients (93.1%) achieved gross total tumor resection. Five patients (17.2%) received radiotherapy after the first operation, and 3 patients (10.3%) had tumor recurrence. None of the patients died. Conclusion Operation is the basis of the treatment of central neurocytoma. It is possible for patients to be cured by total resection of the tumor and protection of normal ventricular structure. Transcortical fistulotomy is a reliable approach for the removal of large central neurocytomas in the ventricle. Patients should be closely observed post-operation, and MRI of the head should be rechecked regularly. If tumor progression occurs, then radiotherapy should be considered.

Pituitary adenomas constitute one of the most common intracranial tumors. MicroRNAs play an important role in development and progression of pituitary adenomas. In this study, we showed that miR-219a-2-3p was significantly down-regulated in pituitary adenomas cells. Overexpression of miR-219a-2-3p suppressed the proliferation and promoted apoptosis of pituitary adenomas cells. After bioinformatics analysis, we found that MDM2 was one of the downstream targets of miR-219a-2-3p. Further researches showed that miR-219a-2-3p could reduce the protein level of MDM2 by binding to the 3ʹ-UTR of MDM2 and promoted p53 expression. Then, we overexpressed both miR-219a-2-3p and MDM2 in the same group and found that it could counteract the effect of overexpressing miR-219a-2-3p alone on proliferation and apoptosis of pituitary adenoma cells. Taken together, these results suggested that miR-219a-2-3p regulated the proliferation and apoptosis by targeting MDM2/p53 in pituitary adenomas. Therefore, miR-219a-2-3p may serve as a novel marker and therapeutic target for pituitary adenomas.

Objective To study the expression of FAM46A in glioblastoma (GBM) and analyze its significance in predicting the prognosis of patients. Materials and methods mRNA expression and clinical data of patients with GBM were retrieved from ONCOMINE databases and The Cancer Genome Atlas (TCGA) database. Immunohistochemistry was performed in a tissue microarray including 110 GBM cases and 12 normal controls to determine the expression of FAM46A protein. Then, Kaplan-Meier curve and Cox regression model were used to investigate the relationship between FAM46A expression and clinical outcome. Coexpressed genes of FAM46A were analyzed by Linked Omics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Upregulated expression of FAM46A was found in both TCGA and our cohort. High FAM46A expression was associated with the poor prognosis of patients with GBM and could be identified as an independent risk factor for overall survival (HR = 1.652, p = 0.022). Further bioinformatics analysis revealed that FAM46A might be involved in cell motility and endoplasmic reticulum proteostasis and stress to promote GBM progression. Conclusion Our findings suggest that increased expression of FAM46A in GBM is a novel biomarker for predicting poor outcome of patients and that targeting FAM46A may serve as a potential therapy for this disease.

As the population ages, the proportion of elderly patients with glioblastomas has increased. Recently, many researchers have focused on the treatments available to and prognoses in elderly patients with glioblastomas.We conducted a retrospective study of glioblastoma patients aged 60 years old or older who were treated at the Neurosurgery Center at Beijing Tiantan Hospital from 2012 to 2014. Their clinical features, immunohistochemical characteristics, treatments, and outcomes were evaluated to determine treatment tolerance and identify prognostic factors.Among the 70 included patients, the median survival time was 15 months. In the univariate analysis, patients who underwent a gross total resection had longer overall survival times than patients who had a subtotal resection (P0.05), and patients who received postoperative adjuvant therapy had longer overall survival times than those with no postoperative adjuvant therapy (P0.05). The expression of the p53 protein significantly affected overall survival. Patients with low p53 protein expression had a median survival of 17 months, whereas those who had high p53 protein expression had a median survival of 11.50 months (P0.05). Undergoing a gross total resection, receiving postoperative adjuvant therapy and having low p53 protein expression were factors that independently contributed to longer overall survival times in multivariate analysis.Maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide significantly prolonged overall survival times and was well tolerated in elderly patients with glioblastomas. In addition, low p53 protein expression was a significant favorable prognostic indicator in this population.

Objective To present our experience with microsurgical technique for patients with giant meningiomas (maximum diameter ≥7 cm) that obstruct the superior sagittal sinus (SSS). Methods All patients who were preoperatively diagnosed (between 2010 and 2014) with giant meningiomas involving the SSS in Ward 10 at the Neurosurgery Department of Beijing Tiantan Hospital were enrolled in this study. Patient charts, imaging findings, and outcomes were examined. Results The study included 6 male and 4 female patients with a mean age of 46.8 ± 10.7 years. The tumor sizes varied from 7 to 12 cm (mean, 8.8 ± 2.0 cm). All patients underwent customized craniotomies, and aggressive surgery for resection of the invaded SSS was performed. Simpson grade I removals were achieved in all cases. No cases of perioperative mortality occurred. Three patients required cranioplasty as a result of a decompressive craniectomy that was performed during the primary surgery. Histologic examinations showed 1 malignant and 9 benign meningiomas. During the follow-up period (mean, 29.0 ± 9.7 months), recurrence/progression occurred in 1 patient, and 1 patient was lost to follow-up. The recent Karnofsky Performance Score was 80 ± 32.3 and was improved in 5 patients and stabilized in 3 patients. In addition, 7 patients lived independently. Conclusions The rigorous preservation of cortical veins, draining veins, and eloquent areas should be implemented during the resection of large tumors that obstruct the SSS. Suitable individualized approaches associated with full exposure and low cerebral perfusion pressure levels after surgery are critical for favorable results, and the reconstruction of the SSS may not be necessary.