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Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull‐down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR‐150‐5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR‐150‐5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR‐150‐5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR‐150‐5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most universal type of primary brain malignant tumour, and the prognosis of patients with GBM is poor. S100A11 plays an essential role in tumour. However, the role and molecular mechanism of S100A11 in GBM are not clear. Here, we found that S100A11 was up‐regulated in GBM tissues and higher S100A11 expression indicated poor prognosis of GBM patients. Overexpression of S100A11 promoted GBM cell growth, epithelial‐mesenchymal transition (EMT), migration, invasion and generation of glioma stem cells (GSCs), whereas its knockdown inhibited these activities. More importantly, S100A11 interacted with ANXA2 and regulated NF‐κB signalling pathway through decreasing ubiquitination and degradation of ANXA2. Additionally, NF‐κB regulated S100A11 at transcriptional level as a positive feedback. We also demonstrated the S100A11 on tumour growth in GBM using an orthotopic tumour xenografting. These data demonstrate that S100A11/ANXA2/NF‐κB positive feedback loop in GBM cells that promote the progression of GBM. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA) regulate a number of cellular processes. Recent studies have indicated that these molecules function in the epithelial-mesenchymal transition (EMT). However, the crucial systematic role of EMT and miRNAs together in glioblastoma (GBM) remains poorly understood. The present study demonstrated that EMT was closely associated with malignant progression and clinical outcome using three independent glioma databases (GSE16011, Rembrandt and The Cancer Genome Atlas). Furthermore, integrated analysis of miRNAs and mRNA profiling in 491 GBM samples revealed an EMT biological process associated with an miRNA profile (19 positively and 18 negatively correlated miRNAs). Among these miRNAs, miR-95 and miR-223 indicated a high level of functional validation, reflecting their positive correlation with EMT. Additionally, the upregulation of miR-95, which was negatively correlated with EMT, inhibited cellular invasion in glioma U251 and LN229 cells and decreased the expression of the mesenchymal marker N-catenin, whereas an miRNA positively correlated with EMT, miR-223, exhibited the opposite effect. Therefore, the results of the present study could further enhance the current understanding of the functions of miRNAs in GBM, indicating that the EMT-specific miRNA signature may represent a novel target for GBM therapy. [ABSTRACT FROM AUTHOR]

Nuclear factor κB (NF-κB) exhibits an important role in inflammation and tumorigenesis. The key regulatory protein of the pathway, RELB Proto-Oncogene, NF-KB Subunit (relB), is overexpressed and associated with the pathogenesis of a variety of malignant tumors. However, the molecular features and clinical signature of relB expression in gliomas remains to be elucidated. The present study obtained the raw sequencing data of 325 glioma samples of all grades from the Chinese Glioma Genome Atlas (CGGA) database and human glioma cell line (LN229) from the Chinese Academy of Sciences cell bank. Cell proliferation, invasion and wound healing assays were used for functional annotation of relB. Western blot analysis was used for validating the protein expression of relB, matrix metalloproteinase (MMP)-2 and MMP-9 in a further 77 glioma samples. In Diffuse Glioma data, relB expression was associated with glioma grade, demonstrated a mesenchymal subtype preference and cell development association. The downregulation of relB expression inhibited glioma cell migration and invasion by regulating the MMPs in vitro. relB expression was independently associated with grade and prognosis of grade III and grade IV gliomas, suggesting that relB is a novel biomarker with therapeutic potential for predicting prognosis in glioma. [ABSTRACT FROM AUTHOR]

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in highgrade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies. [ABSTRACT FROM AUTHOR]

GBM tissues are comprised of not only tumor cells but also tumor-associated nontumor cells, such as stromal cells and immune cells, which dilute the purity of glioma cells and function in glioma biology. However, the roles of miRNAs in modulating glioma purity are not clarified. In total, 838 glioma samples with transcriptome data, including 537 RNAseq data from TCGA project and 301 microarray data from Chinese Glioma Genome Atlas (CGGA project), were recruited into our investigation. Tumor purity, molecular subtypes and IDH status were also available. R language was employed as the main tool for statistical analysis and graphical work. Screening miRNA profiling and paired TCGA samples’ transcriptome data demonstrates that miR-17-5p expression harbors the most significant positive correlation with glioma purity among all miRNAs. CXCL14 shows robust negative correlation with miR-17-5p expression in TCGA and CGGA dataset. miR-17-5p directly targets CXCL14 and functions as a tumor-suppressor of GBM. CXCL14 showed lower expression in proneural subtype and may contribute as a potential marker for proneural subtype in glioma. Genes markedly correlated with CXCL14 are involved in essential functions associated with anti-tumor immune process. CXCL14 has a strong correlation with immune(T cells, Monocytic lineage and Neutrophils) and Fibroblasts within glioma environment. miR-17-5p and CXCL14 exhibited predictive values for high-grade glioma(HGG) patients: Higher miR-17-5p indicated significantly longer survival while lower CXCL14 indicated longer survival. Our results highlight the importance of the miR-17-5p-CXCL14 axis in regulating key steps of anti-tumor immune process and may serve as potential targets of immune treatments for gliomas. [ABSTRACT FROM AUTHOR]

Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objective: The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs., Methods: A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion., Results: Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001)., Conclusions: Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.

Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans' foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells' metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 El Khayari, Bouchmaa, Taib, Wei, Zeng and El Fatimy.)

In this study, we demonstrate that bone mesenchymal stem cell (BMSC)-derived exosomes alter tumor phenotypes by delivering miR-512-5p. miR-512-5p was downregulated in glioblastoma tissues and cells, and Jagged 1 (JAG1) was the target gene of miR-512-5p. We clarified the expression patterns of miR-512-5p and JAG1 along with their interactions in glioblastoma. Additionally, we observed that BMSC-derived exosomes could contain and transport miR-512-5p to glioblastoma cells in vitro . BMSC-derived exosomal miR-512-5p inhibited glioblastoma cell proliferation and induced cell cycle arrest by suppressing JAG1 expression. In vivo assays validated the in vitro findings, with BMSC-exosomal miR-512-5p inhibiting glioblastoma growth and prolonging survival in mice. These results suggest that BMSC-derived exosomes transport miR-512-5p into glioblastoma and slow its progression by targeting JAG1. This study reveals a new molecular mechanism for glioblastoma treatment and validates miRNA packaging into exosomes for glioblastoma cell communication.

Rationale: Glioma stem-like cells (GSCs) contribute to temozolomide (TMZ) resistance in gliomas, although the mechanisms have not been delineated. Methods: In vitro functional experiments (colony formation assay, flow cytometric analysis, TUNEL assay) were used to assess the ability of extracellular vesicles (EVs) from hypoxic GSCs to promote TMZ resistance in glioblastoma (GBM) cells. RNA sequencing and quantitative Reverse Transcription-PCR were employed to identify the functional miRNA in hypoxic EVs. Chromatin immunoprecipitation assays were performed to analyze the transcriptional regulation of miRNAs by HIF1α and STAT3. RIP and RNA pull-down assays were used to validate the hnRNPA2B1-mediated packaging of miRNA into EVs. The function of EV miR-30b-3p from hypoxic GSCs was verified by in vivo experiments and analysis of clinical samples. Results: Hypoxic GSC-derived EVs exerted a greater effect on GBM chemoresistance than those from normoxic GSCs. The miRNA profiling revealed that miR-30b-3p was significantly upregulated in the EVs from hypoxic GSCs. Further, HIF1α and STAT3 transcriptionally induced miR-30b-3p expression. RNA immunoprecipitation and RNA-pull down assays revealed that binding of miR-30b-3p with hnRNPA2B1 facilitated its transfer into EVs. EV-packaged miR-30b-3p (EV-miR-30b-3p) directly targeted RHOB, resulting in decreased apoptosis and increased proliferation in vitro and in vivo . Our results provided evidence that miR-30b-3p in CSF could be a potential biomarker predicting resistance to TMZ. Conclusion: Our findings indicated that targeting EV-miR-30b-3p could provide a potential treatment strategy for GBM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: At present, prostate-specific antigen (PSA) is the primary evaluation index for judging the necessity of prostate cancer (PCa) biopsy. However, there is a high false-positive rate and a low predictive value due to many interference factors. In this study, we tried to find a novel prediction model that could improve the positive rate of prostate biopsy and reduce unnecessary biopsy., Methods: We retrospectively studied 237 patients, including their age, body mass index (BMI), PSA, prostate volume (PV), prostate imaging-reporting and data system (PI-RADS) v2 score, neutrophil-lymphocyte ratio (NLR), biopsy Gleason score (BGS), and other information. The univariate and multivariate logistic analyses were used to screen out indicators related to PCa. After establishing a prediction formula model, we used receiver operating characteristic (ROC) curves to assess its prediction performance., Results: Our study found that age, PSA, PI-RADS v2 score, and diabetes significantly correlated with PCa. Based on multivariate logistic regression analysis results, we created the following prediction formula: Y = 2.599 × PI-RADS v2 score + 1.766 × diabetes + 0.052 × age + 1.005 × PSAD - 9.119. ROC curves showed the formula's threshold was 0.3543. The composite formula had an excellent capacity to detect PCa with the area under the curve (AUC) of 0.91. In addition, the composite formula also achieved significantly better sensitivity, specificity, and diagnostic accuracy than PSA, PSA density (PSAD), and PI-RADS v2 score alone., Conclusions: Our predictive formula predicted performance better than PSA, PSAD, and PI-RADS v2 score. It can thus contribute to the diagnosis of PCa and be used as an indicator for prostate biopsy, thereby reducing unnecessary biopsy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau.2019.12.42). The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Long non-coding RNAs (lncRNAs) have great value in research on tumour targeted therapy, including for glioma. In the present study, we investigated the role of the lncRNA deleted in lymphocytic leukaemia 2 (lncRNA-DLEU2) in glioma. First, we found that lncRNA-DLEU2 is highly expressed in glioma tissues and cell lines. Next, experiments in cells showed that lncRNA-DLEU2 knockdown inhibited, whereas lncRNA-DLEU2 overexpression promoted, the clone formation, migration and invasion of glioma cells. A luciferase reporter assay and an RNA immunoprecipitation assay demonstrated that lncRNA-DLEU2 acts as a sponge for miR-186-5p in glioma cells. Further, studies suggested that miR-186-5p inhibits the expression of PDK3, which is an oncogene in glioma. Moreover, with rescue experiments, we demonstrated that lncRNA-DLEU2 regulates the expression of PDK3 and the progression of glioma in a miR-186-5p-dependent manner. Finally, we also showed that lncRNA-DLEU2 promotes glioma growth in a manner that is related to miR-186-5p and PDK3 in vivo . In conclusion, our study reported for the first time that lncRNA-DLEU2 promotes glioma progression by targeting the miR-186-5p/PDK3 axis. These findings provide novel strategies for the gene therapy treatment of glioma., Competing Interests: None.

In recent years, many studies have reported on the abnormal expression and correlation of long non-coding RNAs (lncRNAs) in tumours. However, the accurate molecular mechanism of lncRNAs in glioma is still in its infancy. In the present study, we aimed to explore the molecular mechanism of small nucleolar RNA host gene 5 (SNHG5) in glioma progression. First, we found that SNHG5 expression was higher in glioma and was related to glioma glucose uptake, migration and invasion. Second, through a series of assays, we concluded that SNHG5 acts as a sponge for miR-205, which inhibits tumour growth in glioma by targeting E2F transcription factor 3 (E2F3). Third, using a xenograft mouse model, we demonstrated that SNHG5 regulates tumourigenesis in vivo Taken together, our results show that the SNHG5/miR-205/E2F3 axis is involved in glioma progression and may provide a new therapeutic target for the diagnosis and therapy of glioma., (© 2019 The Author(s).)

Background/aims: Glioma is one of the most devasting tumors and confers dismal prognosis. Long noncoding RNAs(lncRNAs) have emerged as important regulators in various tumors including glioma. A classic lncRNA-H19, which is found to be highly expressed in human glioma tissues and cell lines, and is associated with tumor progression thus predicating clinical outcomes in glioma patients. However, the overall biological functions and their mechanism of H19 in glioma are not fully understood., Methods: Firstly, we analyzed H19 alterations in different grades of glioma tissues through an analysis of 5 sequencing datasets and qRT-PCR was performed to confirm the results. Next, we evaluated the effect of H19 on glioma cells migration, invasion and EMT process. Luciferase assays and RIP assays were employed to figure out the correlation of H19 and SOX4., Results: H19 was overexpressed in glioma tissues. Down-regulation of H19 led to the inhibition of migration, invasion and EMT process with a reduction in N-cadherin and Vimentin. H19 and SOX4 are both direct target of miR-130a-3p. H19 could compete with SOX4 via sponging miR-130a-3p., Conclusion: Taken together, these results provide a possible function of H19 as an oncogene in glioma tissues and provide a potential new therapeutic strategy for human glioma., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro . Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R 2 =0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Polycomb group (PcG) proteins form at least two key complexes, namely polycomb repressive complex 1 and polycomb repressive complex 2. These complexes are involved in the progression of various cancers. Systematic research has not been conducted on the aberrant expression of PcG members in gliomas. Using the Chinese Glioma Genome Atlas data set, PcG expression patterns between normal brain tissues and glioma samples were analyzed, and a PcG-based classifier was then developed using BRB Cox regression and risk-score model. These results were validated in an independent GSE16011 set. A total of six PcGs [chromobox protein homolog (CBX) 6, CBX7, PHD finger protein 1, enhancer of zeste homolog 2 (EZH2), DNA (cytosine-5-)-methyltransferase 3β (DNMT3B) and polyhomeotic-like protein 2] were identified to be associated with glioma grade. Survival analysis then revealed a five-PcG gene signature one protective gene (enhancer of zeste homolog 1) and four risky genes (EZH2, PHD finger protein 19, DNMT3A and DNMT3B), which may identify patients with high risk of poor prognosis of glioma. Multivariate Cox analysis indicated that the five-PcG signature was an independent prognostic biomarker. These findings indicated that a novel prognostic classifier, five-PcG signature, served as an independent prognostic marker for patients with glioma.

Background: Gliomas are based on a genetic abnormality and present with a dismal prognosis. MicroRNAs (miRNAs) are considered to be important mediators of gene expression in glioma tissues., Methods: Real-time PCR was used to analyze the expression of microRNA-423-5p (miR-423-5p) in human glioma samples and normal brain tissue. Apoptosis, cell cycle, proliferation, immunostaining, transwell, in vitro 2D and 3D migration, and chemosensitivity assays were performed to assess the phenotypic changes in glioma cells overexpressing miRNA-423-5p. Western blotting was used to determine the expression of inhibitor of growth 4 (ING-4)in glioma tissues, and a luciferase reporter assay was conducted to confirm whether ING-4 is a direct target of miR-423-5p. Western blotting was used to identify the potential signaling pathways that are affected in glioma cell growth by miR-423-5p. Xenograft tumors were examined in vivo for the carcinogenic effects of miR-423-5p in glioma tissues., Results: We first reported that miR-423-5p expression was increased in gliomas and was a potential tumor promoter via targeting ING-4. The overexpression of miR-423-5p resulted in upregulation of important signaling molecules such as p-AKT and p-ERK1/2. In clinical samples, miR-423-5p was dysregulated, and a corresponding alteration in ING-4 expression was observed (P = .0207). Furthermore, the overexpression of miR-423-5p strengthened glioma cell proliferation, angiogenesis, and invasion. Finally, miR-423-5p overexpression also strengthened GBM neurosphere formation and rendered glioma cells resistant to temozolomide (TMZ)., Conclusion: This study establishes that miR-423-5p functions as an oncogene in glioma tissues by suppressing ING-4 and suggests that it has therapeutic potential for glioma., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current World Health Organization (WHO) classification of human gliomas is mainly based on morphology. However, it has limitations in prognostic prediction. We examined whether combining isocitrate dehydrogenase (IDH) 1/2 mutation status with the Ki-67 labeling index would improve the definition of prognostically distinct entities. We investigated the correlation of Ki-67 expression with IDH1/2 mutation status and their impact on clinical outcome in 703 gliomas. Low Ki-67 expression closely overlapped with IDH1/2 mutation in our cohort (P < 0.0001). Patients with IDH1/2 mutation survived significantly longer than patients with wild-type IDH1/2 did (P < 0.0001); higher Ki-67 expression was associated with shorter progression-free survival and overall survival (OS) (P < 0.0001). IDH1/2 combined with Ki-67 was used to re-classify glioma patients into five groups. IDH1/2 mutant patients with low and moderate Ki-67 expression (Group1) had the best prognosis, whereas patients with wild-type IDH1/2 and high Ki-67 expression (Group5) had the worst prognosis (Median OS = 1527 vs. 355 days, P < 0.0001). To summarize, our new classification model distinguishes biologically distinct subgroups and provides prognostic information regardless of the conventional WHO grade. Classification based on IDH1/2 mutation status and Ki-67 expression level could be more convenient for clinical application and guide personalized treatment in malignant gliomas.