Background: The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer. This report analyzed the involvement of a key glycolytic enzyme, alpha-enolase (ENO1), in tumor progression and prognosis of human glioma.Methods: ENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice.Results: ENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression.Conclusion: Overexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.

The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells.

The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O⁶-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

Background: Age is associated with the prognosis of glioma patients, but there is no uniform standard of age-group classification to evaluate the prognosis of glioma patients. In this study, we aimed to establish an age group classification for risk stratification in glioma patients. Methods: 1502 patients diagnosed with gliomas at Nanfang Hospital between 2000 and 2018 were enrolled. The WHO grade of glioma was used as a dependent variable to evaluate the effect of age on risk stratification. The evaluation model was established by logistic regression, and the Akaike information criterion (AIC) value of the model was used to determine the optimal cutoff points for age-classification. The differences in gender, WHO grade, pathological subtype, tumor cell differentiation, tumor size, tumor location, and molecular markers between different age groups were analyzed. The molecular markers included GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status. Results: The proportion of men with glioma was higher than that of women with glioma (58.3% vs 41.7%). Analysis of age showed that appropriate classifications of age group were 0–14 years old (pediatric group), 15–47 years old (youth group), 48–63 years old (middle-aged group), and ≥ 64 years old (elderly group).The proportions of glioblastoma and large tumor size (4–6 cm) increased with age (p = 0.000, p = 0.018, respectively). Analysis of the pathological molecular markers across the four age groups showed that the proportion of patients with larger than 10% area of Ki-67 expression or positive PR expression increased with age (p = 0.000, p = 0.017, respectively). Conclusions: Appropriate classifications of the age group for risk stratification are 0–14 years old (pediatric group), 15–47 years old (young group), 48–63 years old (middle age group) and ≥ 64 years old (elderly group). This age group classification is effective in evaluating the risk of glioblastoma in glioma patients.

Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor heterogeneity, along with considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as in vitro cell cultures and in vivo animal models, demonstrate significant limitations that fall short of satisfying the research requisites. Patient-derived tumor organoids, which recapitulate the structures, specific functions, molecular characteristics, genomics alterations and expression profiles of primary tumors. They have been efficaciously implemented in illness portrayal, mechanism exploration, high-throughput drug screening and assessment, discovery of innovative therapeutic targets and potential compounds, and customized treatment regimen for cancer patients. In contrast to conventional models, tumor organoids offer an intuitive, dependable, and efficient in vitro research model by conserving the phenotypic, genetic diversity, and mutational attributes of the originating tumor. Nevertheless, the organoid technology also confronts the bottlenecks and challenges, such as how to comprehensively reflect intra-tumor heterogeneity, tumor microenvironment, tumor angiogenesis, reduce research costs, and establish standardized construction processes while retaining reliability. This review extensively examines the use of tumor organoid techniques in fundamental research and precision medicine. It emphasizes the importance of patient-derived tumor organoid biobanks for drug development, screening, safety evaluation, and personalized medicine. Additionally, it evaluates the application of organoid technology as an experimental tumor model to better understand the molecular mechanisms of tumor. The intent of this review is to explicate the significance of tumor organoids in cancer research and to present new avenues for the future of tumor research.

Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma