Ambiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring. We conducted 1H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the 1H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9. Stable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells’ malignant behaviors. Our results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring.

The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment.

Background: LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma. Methods: Using real-time PCR and immunohistochemistry, we detected the mRNA and protein expression of LATS1 in glioma. The effect of LATS1 on cell growth and invasion were investigated. Results: We found that mRNA and protein of LATS1 expression is significantly downregulated in glioma compared with normal control brain tissues. Furthermore, reduced LATS1 expression was markedly negatively correlated with WHO grade and KPS (p<0.001 and p<0.001) in glioma patients. Patients with lower LATS1 expression had a significantly shorter overall survival time than did patients with higher LATS1 expression. Multivariate analysis suggested that the level of LATS1 expression was an independent prognostic indicator (p<0.001) for the survival of patients with glioma. Forced expression of LATS1 in glioma U251 cells not only significantly suppressed cell growth, migration and invasion, but retarded cell cycle progression from G2/M to G1 in vitro. Finally, we found that overexpressed LATS1 markedly inhibited the expression level of cell cycle factor CCNA1. Conclusion: These results indicate that LATS1 is an important candidate tumor suppressor and its downregulated expression may contribute to glioma progression.

Sirtuin7 (Sirt7) is a member of the Sir2 histone deacetylase family that functions in a number of physiological processes, including cellular metabolism, ageing and apoptosis. Several studies have indicated that Sirt7 may serve a vital role in promoting the development of cancer. However, to the best of our knowledge, its function in glioma progression has not been demonstrated. The present study revealed that Sirt7 expression was upregulated in human glioma tissues and that the high expression level of Sirt7 was positively associated with glioma malignancy. Further results indicated that the suppression of Sirt7 expression could inhibit the activation of phosphorylated extracellular signal‑regulated kinase (p‑ERK) concomitantly with decreased expression of cyclin‑dependent kinase 2 in glioma cells. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) inhibited when Sirt7 was downregulated by siRNA interference in glioma cell lines. The findings of the present study indicated that Sirt7 affects the malignancy of glioma cells mainly in promoting glioma proliferation and invasion through ERK and STAT3 signaling. Thus, Sirt7 may function as a valuable target for the treatment of human glioma.

L‑type amino acid transporter 1 (LAT1) has emerged as a critical molecular target for advancing boron neutron capture therapy (BNCT), a promising treatment that leverages selective boron accumulation and neutron irradiation to eradicate cancer cells. The frequent upregulation of LAT1 in aggressive tumors (such as gliomas and specific subtypes of lung and breast cancer) underpins its essential role as the principal mediator of tumor‑selective boron compound uptake in BNCT. The present review comprehensively examines the structure and function of LAT1, the mechanistic principles of boron transport (including LAT1 mediation) and the key regulatory pathways governing BNCT efficacy. Building on this and given the role of LAT1 in reprogramming tumor metabolism through amino acid transport, advanced metabolomics tools, particularly liquid chromatography‑mass spectrometry and nuclear magnetic resonance, offer a novel approach for clarifying the contribution of LAT1 to BNCT. These techniques hold significant potential to map metabolic profiles altered by LAT1‑mediated boron compound uptake, thereby elucidating downstream biochemical consequences relevant to the therapeutic efficacy and resistance mechanisms. Synthesizing the dual role of LAT1 as both a vulnerability and therapeutic target in BNCT, the present review systematizes key challenges, including the need for selective boron compounds, resistance mechanisms and off‑target effects, while mapping actionable pathways to unlock its potential via refined regulation strategies, next‑generation delivery agents and personalized approaches. By addressing these knowledge gaps, this synthesis provides a foundational framework to harness LAT1‑targeted BNCT, offering potential to advance precision oncology paradigms and improve clinical outcomes for patients with LAT1‑enriched tumors.

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