In recent years, long non-coding RNAs (lncRNAs) have been shown to play important regulatory roles in cellular processes. Growth arrests specific transcript 5 (GAS5) is a lncRNA that is highly expressed during the cell cycle arrest phase but is downregulated in actively growing cells. Growth arrests specific transcript 5 was discovered to be downregulated in several cancers, primarily solid tumors, and it is known as a tumor suppressor gene that regulates cell proliferation, invasion, migration, and apoptosis via multiple molecular mechanisms. Furthermore, GAS5 polymorphism was found to affect GAS5 expression and functionality in a cell-specific manner. This review article focuses on GAS5’s tumor-suppressive effects in regulating oncogenic signaling pathways, cell cycle, apoptosis, tumor-associated genes, and treatment-resistant cells. We also discussed genetic polymorphisms of GAS5 and their association with cancer susceptibility.

Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients’ survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.

Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer–macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis.

Gliomas are aggressive brain tumours with diverse histological and molecular features, complicating accurate diagnosis and treatment. Dysregulated lipid metabolism contributes to glioma progression, and analysing lipid profiles in plasma and tissue may enhance diagnostic and prognostic accuracy. This study investigated lipid dysregulation to identify key lipid signatures that distinguish glioma from other brain diseases and examined the associations between lipid biomarkers in glioma tissue and plasma. Biospecimens from 11 controls and 72 glioma patients of varying grades underwent lipidomic profiling using liquid chromatography-mass spectrometry. Univariate and multivariate analyses identified differentially abundant lipids, and correlation analysis evaluated the associations between tissue and plasma biomarkers. Lipidomic analysis revealed distinct lipid profiles in the tissues and plasma of glioma patients compared to those of controls. Prominent lipid metabolites in glioma tissues included LPC 21:3 (AUC = 0.925), DG 43:11 (AUC = 0.906), and PC 33:1 (AUC = 0.892), which served as effective biomarkers. Conversely, in plasma, lipid metabolites such as phosphatidylethanolamine (PE 21:3, AUC = 0.862), ceramide-1-phosphate (CerP 26:1, AUC = 0.861), and sphingomyelin (SM 24:3, AUC = 0.858) were identified as the most promising lipid biomarkers. Significant positive and negative correlations were observed between the tissue and plasma lipid biomarkers of glioma patients. Lipidomic profiling revealed aberrant lipid classes and pathways in glioma tissues and plasma, enhancing understanding of glioma heterogeneity and potential clinical applications.

Glioblastoma multiforme (GBM) are the major death contributor in primary brain tumour. Despite having an improved diagnostic criterion by integrating both histological and molecular features such as Isocitrate Dehydrogenase (IDH) detection, the prognosis of GBM patients still remain poor. Lipid metabolism is an essential pathway that fuel GBM aggressiveness. IDH1 one of the key enzyme that regulates it. Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) in tumour initiation and progression. In parallel, miRNA-mediate ceRNA crosstalk between lncRNAs and mRNAs. In this study, we aim to investigate the IDH1 subgroup lncRNA associated ceRNA network hub gene responsible in the coordination of glioblastoma multiforme lipid metabolism using bioinformatics approach. TCGA-GBM dataset consist of 168 GBM RNA-seq (159 IDH1 wt and 9 IDH1 mutation) were downloaded. Differentially expressed genes (DEG) were then obtained using Limma. Gene sets related with lipid metabolism from GSEA-MSigDB were overlapped with DEG using Venn diagram to identify the DEmRNA that are related with lipid metabolism. Construction of mRNA-miRNA and lncRNA-miRNA interaction networks were performed using miRNet. The ceRNA interaction network were later combined in the Cytoscape software. Potential lncRNA hub genes were identified by CytoHubba analysis. From 1389 DEG, 67 genes were identified to be significant in the regulation of lipid metabolism. By analysing the lncRNA-miRNA-mRNA interaction network, candidate hub lncRNAs consists of three genes with highest connective nodes; CYTOR, LOXL1-AS1 and HOTAIR. These genes are significantly upregulated in glioma. LOXL1-AS1 serve as an excellent prognostic biomarker for both glioma and glioblastoma as the effect of high and low LOXL1-AS1 expression on patients’ survival is significant (p<0.05). Data mining and bioinformatics approach guided the identification of the potential hub lncRNAs associated ceRNA network in GBM lipid metabolism. This allows us to uncover the novel role of lncRNA in GBM tumorigenesis.