Construction of immune cell infiltration protein network based on clinical low grade glioma cases.

Many researchers have studied low-grade glioma and the immune microenvironment have been studied by many researchers. Recent studies suggest that macrophages and dendritic cells trigger part of the local immune dysregulation in the tumor microenvironment, and they have been polarized into a mixed pro-inflammatory and immunosuppressive phenotype. It is suggested that the degree of immune infiltration is related to the survival, therapeutic effect, and prognosis of patients. This opens up new avenues for cancer treatment. On the basis of immune infiltration degree, a protein interaction network (PIN) and a prognosis model were established, and we chose the top 20 pathways from enrichment analysis to provide potential targets for glioma clinical treatment.

Percutaneous full-endoscopic uniportal decompression for the treatment of symptomatic idiopathic lumbar spinal epidural lipomatosis: Technical note.

Background: Lumbar spinal epidural lipomatosis (SEL) is a rare condition characterized by an excessive accumulation of adipose tissue within the spinal canal, compressing the dura sac and/or nerve roots. When conservative treatments fail and clinical symptoms progress quickly and seriously, surgical decompression should be considered. With the rapid development of endoscopic armamentaria and techniques, the pathological scope that can be treated by percutaneous endoscopic spine surgery is ever expanding. Objective: In this paper, the authors describe a patient with lumbar spinal epidural lipomatosis who was treated with a percutaneous full-endoscopic uniportal decompression surgery successfully. This article aims to validate the feasibility of percutaneous full-endoscopic uniportal decompression for the treatment of symptomatic idiopathic spinal epidural lipomatosis via interlaminar approach. Methods: We describe a case of a 69-year-old man with a 10-year history of low back pain, intermittent claudication, and bilateral leg neuropathic pain. He was diagnosed with lumbar epidural lipomatosis, which did not respond to conservative therapy. After a comprehensive evaluation, he underwent percutaneous endoscopic spine surgery to remove hyperplastic adipose tissue and decompress nerve roots and dura sac. Results: The patient was treated with a percutaneous full-endoscopic uniportal decompression surgery successfully. After the procedure, his leg pain decreased and his walking capacity improved. There were no surgery-related complications, such as cerebrospinal fluid leakage, incision infection, etc. Conclusions: The case with SEL was successfully treated with a percutaneous full-endoscopic uniportal surgery, which has the advantages of excellent presentation of anatomical structures, expanded field of vision, less surgical-related trauma, and bleeding. The key point of the procedure is to release and cut off the bands which divide the epidural space into small rooms filled with excess adipose tissue.

Percutaneous Full-Endoscopic C2 Ganglionectomy for the Treatment of Intractable Occipital Neuralgia: Technical Note.

BACKGROUND: The C-2 dorsal root ganglionectomy procedure can provide effective treatment for intractable occipital neuralgia (ON). However, the traditional microsurgery of C2 ganglionectomy needs a wide incision and significant paraspinous muscle dissection for adequate visualization. The indications of endoscopic spine surgery are ever expanding, with the development of endoscopic armamentaria and technological innovations. OBJECTIVE: To validate the feasibility of the approach and describe several operative nuances based on the authors' experience. In this paper, the authors describe a patient with intractable ON who was successfully treated with a percutaneous full-endoscopic C2 ganglionectomy. METHODS: We describe the case of an 83-yr-old female with a 2-yr history of left ON who did not respond to a series of treatments, including physical therapy, drug therapy, injection therapy, and radiofrequency therapy. After careful examination, we performed a percutaneous, full-endoscopic left C2 ganglionectomy. RESULTS: The patient was successfully treated with a percutaneous full-endoscopic ganglionectomy. Afterwards, her intractable and constant pain was relieved. There was no cerebrospinal fluid leakage, incision infection, neck deformity, or other complications. CONCLUSION: C2 ganglionectomy can be accomplished successfully using a full-endoscopic uniportal surgical technique under continuous irrigation, which has the advantages of excellent illumination and visualization, reduced surgery-related trauma, and reduced bleeding.

HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels.

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.

Long noncoding RNA HNF1A-AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR-363-3p/MAP2K4.

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A-AS1 was increased in glioma tissues and cells. Knockdown of HNF1A-AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR-363-3p in glioma tissues and cell lines. The interaction between HNF1A-AS1 and miR-363-3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A-AS1 and miR-363-3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR-363-3p. The expression of MAP2K4 was negatively correlated with miR-363-3p while positively related to HNF1A-AS1 in glioma tissues. We also found the regulatory effect of HNF1A-AS1 on the MAP2K4-dependent JNK signaling pathway. All findings indicated that HNF1A-AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR-363-3p sponge.

RAD21 inhibited transcription of tumor suppressor MIR4697HG and led to glioma tumorigenesis.

BACKGROUND: Studies have revealed the aberrant expression of lncRNAs is responsible for human carcinogenesis. MIR4697 host gene (MIR4697HG) is an upregulated lncRNA that promoted cell growth and metastasis in other cancers. In this study, we tested the expression of MIR4697HG in glioma cells and detected the comparatively down-regulated expression. RAD1 is an upstream regulator for MIR4697HG. This study aimed at exploring the regulatory mechanism and function of RAD1/MIR4697HG/PRR12 axis in glioma. METHODS: We profiled the expression of MIR4697HG in glioblastoma multiforme (GBM) tissues according to GEPIA database as well as in glioma cells by qPCR. Functional experiments confirmed relevant role of MIR4697HG in regulating glioma cell proliferation and migration. We also carried out luciferase reporter assay, pull down assay and RIP assay to verify the location and interaction among the indicated RNA molecules. RESULTS: The expression of MIR4697HG is down-regulated significantly in glioma cells due to the up-regulated expression of RAD21. MiR-766-5p was identified functioning as a sponge for MIR4697HG and is sequestered by MIR4697HG. We also found either miR-766-5p inhibitor or PRR12 knockdown rescued the function depletion caused by MIR4697HG overexpression. In all, the down-regulated expression of MIR4697HG inhibited PRR12 to suppress glioma and led to the deterioration of glioma. CONCLUSION: RAD21-induced down-regulated expression of MIR4697HG is correlated with aggravation of glioma. The MIR4697HG/miR-766-5p/PRR12 axis predicts poor results in glioma and MIR4697HG could be considered as a promising biomarker for diagnosis and treatment of glioma.

PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10.

Long noncoding RNAs (lncRNAs) get great involvements in the development of countless cancers. Nonetheless, the deep molecular mechanism by which lncRNA regulates the formation of glioma is unclear. In our study, the expression of PSMB8-AS1 was dramatically upregulated in glioma tissues and cells, further, PSMB8-AS1 silencing restrained cell proliferation in glioma, and the results of PSMB8-AS1 overexpression were opposite. Moreover, PSMB8-AS1 could bind with miR-574-5p, which was low expressed in glioma cells. In addition, RAB10 acted the target gene of miR-574-5p, and PSMB8-AS1 could regulate RAB10 via modulating miR-574-5p. Besides, miR-574-5p inhibitor/mimics remedied the repressive/simulative role of PSMB8-AS1 depletion/overexpression, and RAB10 downregulation/upregulation reversed the encouraging/blocked function caused by miR-574-5p inhibitor/mimics in PSMB8-AS1 depletion/overexpression transfected glioma cells. Additionally, ELK1, a transcription factor, could active PSMB8-AS1 expression. To be concluded, PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10, which may be contributory to find new targets to treat glioma.

ß1,6 GlcNAc branches-modified protein tyrosine phosphatase Mu attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways.

The metastatic potential of malignant tumor has been shown to be correlated with the increased expression of tri- and tetra-antennary ß1,6-N-acetylglucosamine (ß1,6-GlcNAc) N-glycans. In this study, We found that GnT-V expression was negatively correlated with receptor protein tyrosine phosphatase type µ(RPTPµ) in human glioma tissues. To study whether RPTPµ is a novel substance of GnT-V which further affect RPTPµ's downstream dephosphorylation function, we preform lentiviral infection with GnT-V gene to construct stably transfected GnT-V glial cell lines. We found RPTPµ undergone severer cleavage in GnT-V transfected glioma cells compare to Mock cells. RPTPµ intracellular domain fragments increased while ß1,6-GlcNAc-branched N-glycans increased, in consistent with the decrease of RPTPµ's catalytic activity. The results showed that abnormal glycosylation could decrease the phosphorylation activity of PTP µ, and affect PLCγ-PKC pathways. Both protease inhibitor Furin and N-glycan biosynthesis inhibitor swainsonine could decrease cell mobility in GnT-V-U87 transfectants and other glioma cell lines. All results above suggest increased post-translational modification of RPTPµ N-glycans by GnT-V attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways, and that the ß1,6-GlcNAc-branched N-glycans of RPTPµ play a crucial role in glioma invasivity.

Long noncoding RNA FAM83H-AS1 exerts an oncogenic role in glioma through epigenetically silencing CDKN1A (p21).

Gliomas are the commonest and most aggressive primary malignant tumor in the central nervous system. Long noncoding RNAs (lncRNAs) have been identified to act as crucial regulators in multiple biological processes, including tumorigenesis. FAM83H antisense RNA1 (FAM83H-AS1) has been uncovered to be dysregulated in several cancers. However, the biological role of FAM83H-AS1 in glioma still needs to be investigated. Currently, our findings indicated that FAM83H-AS1 was upregulated in glioma tissues and cell lines and high level of FAM83H-AS1 was associated with poor prognosis of glioma. Loss-of-function assays demonstrated that silenced FAM83H-AS1 obviously suppressed cell proliferation via regulating the cell-cycle distribution and cell apoptosis rate, and mechanistic experiments revealed that FAM83H-AS1 could epidemically silence CDKN1A expression through recruiting EZH2 to the promoter of CDKN1A, thereby influencing the cell cycle and proliferation. Collectively, our findings suggested that FAM83H-AS1 participated in the progression of glioma and might act as a potential therapeutic target and prognosis biomarker for human glioma.

Image-guided chemotherapy with specifically tuned blood brain barrier permeability in glioma margins.

Blood-brain barrier (BBB) disruption is frequently observed in the glioma region. However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose. Method: A tumor vasculature-targeted nanoagonist was developed. Glioma targeting specificity of the nanoagonist was evaluated by in vivo optical imaging. BBB permeability at the glioma margin was quantitatively measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Single-photon emission computed tomography imaging/computed tomography (SPECT/CT) quantitatively determined the glioma uptake of the radiolabeled model drug. T2-weighted MRI monitored the tumor volume. Results: Immunostaining studies demonstrated that the BBB remained partially intact in the invasive margin of patients' gliomas regardless of their malignancies. DCE-MRI showed that vascular permeability in the glioma margin reached its maximum at 45 min post nanoagonist administration. In vivo optical imaging indicated the high glioma targeting specificity of the nanoagonist. SPECT/CT showed the significantly enhanced glioma uptake of the model drug after pre-treatment with the nanoagonist. Image-guided paclitaxel injection after nanoagonist-mediated BBB modulation more efficiently attenuated tumor growth and extended survival than in animal models treated with paclitaxel or temozolomide alone. Conclusion: Thus, image-guided drug delivery following BBB permeability modulation holds promise to enhance the efficacy of chemotherapeutics to glioma.

N-Glycosylation at Asn 402 Stabilizes N-Cadherin and Promotes Cell-Cell Adhesion of Glioma Cells.

Cadherin is crucial for cell-cell adhesion and N-glycosylation of N-cadherin has been implicated in the process of mammary, renal, and ovarian carcinogenesis. However, whether N-glycosylation of N-cadherin plays a role in glioma remains unknown. Previous studies had indicated that N-glycosylation could occur at three asparagine residues of N-cadherin. By generating and over-expressing N-glycosylation-deficient N-cadherin mutants in the human glioma cell lines SHG66 and U87, we found that mutation of N402 but not of the other potentially N-glycosylated residues destabilized N-cadherin and led to its ubiquitylation and subsequent proteasomal degradation. Furthermore, destabilized N-cadherin inhibited cadherin-mediated cell-cell adhesion and promoted cell migration. Our findings reveal that N-glycosylation controls N-cadherin stability and plays a role in glioma migration. J. Cell. Biochem. 118: 1423-1431, 2017. © 2016 Wiley Periodicals, Inc.

Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression.

Glioblastoma multiforme (GBM) is a severe and highly lethal brain cancer, which malignancy largely stems from its growing in a relatively restrained area in the brain. Hence, the understanding of the molecular regulation of the growth of GBM is critical for improving its treatment. Dysregulation of microRNAs (miRNAs) has recently been shown to contribute to the development of GBM, whereas the role of miR-133 in GBM is unknown. Here, by qualitative reverse transcription polymerase chain reaction (RT-qPCR), we detected lower miR-133 levels in GBM tissues, compared to the paired normal brain tissue. We overexpressed or inhibited miR-133 in GBM cells. Cell growth and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. We found that overexpression of miR-133 decreased GBM cell growth and increased cell apoptosis, while depletion of miR-133 increased cell growth and decreased cell apoptosis. Bioinformatic analysis was performed, showing that miR-133 may target the 3'-untranslated region (3'-UTR) of the epidermal growth factor receptor (EGFR) that transduces cell growth signals. Further, the protein translation inhibition of EGFR by miR-133 was confirmed by a dual luciferase reporter assay. Together, these data suggest that reduced miR-133 levels in GBM tissues promotes cell growth and decreases cell apoptosis, possibly through targeting mRNA of EGFR to suppress its translation.

Neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury in patients with traumatic brain injury.

BACKGROUND: Recent studies have shown that urinary neutrophil gelatinase-associated lipocalin (NGAL) is rapidly up-regulated early after murine renal injury, and in patients after cardiac surgery or patients critically ill with multiple trauma. In this study, we evaluated urinary NGAL levels as a potential biomarker of early acute kidney injury (AKI) in patients with severe traumatic brain injury (TBI). METHODS: All patients with severe TBI admitted to our neurosurgical intensive care unit from March to September 2011 were enrolled prospectively. Urinary NGAL was measured using a chemiluminescent microparticle immunoassay upon admission and at 24 and 48 hours after TBI. The presence of AKI was defined by the Acute Kidney Injury Network (AKIN) criteria. RESULTS: Using AKIN criteria, a total of 13 patients were identified with AKI, an incidence of 24%. Those who subsequently developed AKI had a striking rise in urinary NGAL early after TBI and a sustained increase over the entire duration of the study. The urinary NGAL level of the AKI group was significantly higher than the group without AKI at all time points. Using a cutoff value of 53.9 ng/mL, the area under the receiver-operating characteristic curve for urinary NGAL at 48 hours was 0.876 with a sensitivity of 0.69 and specificity of 0.95. CONCLUSIONS: Increased urinary NGAL is associated with an increased occurrence of AKI in patients with severe TBI. It is possible that urinary NGAL could provide a screening tool for AKI immediately after severe TBI, and this may in turn allow early intervention to ameliorate the adverse effects of AKI.