A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.

Increasing evidence suggests the oncogenic role of missense mutation (AKT1-E17K) of AKT1 gene in meningiomas. Upon investigating the connection between the pro-tumorigenic role of AKT1-E17K and cellular metabolic adaptations, elevated levels of glycolytic enzyme hexokinase 2 (HK2) was observed in meningioma patients with AKT1-E17K compared to patients harboring wild-type AKT1. In vitro experiments also suggested higher HK2 levels and its activity in AKT1-E17K cells.

PRMT1 driven PTX3 regulates ferritinophagy in glioma.

Mutations in the Krebs cycle enzyme IDH1 (isocitrate dehydrogenase (NADP(+)) 1) are associated with better prognosis in gliomas. Though IDH1 mutant (IDH1) tumors are characterized by their antiproliferative signatures maintained through hypermethylation of DNA and chromatin, mechanisms affecting cell death pathways in these tumors are not well elucidated. On investigating the crosstalk between the IDH1 mutant epigenome, ferritinophagy and inflammation, diminished expression of PRMT1 (protein arginine methyltransferase 1) and its associated asymmetric dimethyl epigenetic mark H4R3me2a was observed in IDH1 gliomas.

Brg1 mutation alters oxidative stress responses in glioblastoma.

Increasing evidences suggest that the SWI/SNF chromatin remodeling complex involved in the organization of chromatin architecture via ATP hydrolysis, plays an important role in human cancer. As TCGA gene expression analyses revealed signature of enhanced oxidative stress in GBMs harbouring Brg1mutations, we examined the involvement of ATPase subunit of BRG1 in regulating oxidative stress responses in glioma. BRG1-MUT overexpressing glioma cells exhibit intrinsically higher reactive oxygen species (ROS) levels as compared to BRG1-WT.

Rewiring of Lactate-Interleukin-1β Autoregulatory Loop with Clock-Bmal1: a Feed-Forward Circuit in Glioma.

A desynchronized circadian rhythm in tumors is coincident with aberrant inflammation and dysregulated metabolism. As their interrelationship in cancer etiology is largely unknown, we investigated the link among the three in glioma. The tumor metabolite lactate-mediated increase in the proinflammatory cytokine interleukin-1β (IL-1β) was concomitant with elevated levels of the core circadian regulators Clock and Bmal1.