Effect of IDH3a on glucose uptake in lung adenocarcinoma: A pilot study based on [¹⁸F]FDG

Abstract

Subunit of isocitrate dehydrogenase 3 (IDH3a) as upstream of the hypoxia‐inducible factor was reported highly expressed in malignant tumors, playing an important role in glucose metabolism reprogramming. As one of rate‐limiting enzyme in the Krebs cycle, whether high expression of IDH3a affects glucose uptake in tumors has not been elucidated. This study was aimed to investigate the relationship between IDH3a expression and tumor glucose uptake. Sixty‐five patients who underwent 2‐[ 18 F]‐2‐deoxy‐D‐glucose ([ 18 F]‐FDG) positron emission tomography/computed tomography (PET/CT) imaging before surgery and pathologically diagnosed as lung adenocarcinoma were included. All patients were divided into high (n = 31) and low (n = 34) groups according IDH3a expression by immunohistochemistry. Comparatively higher [ 18 F]‐FDG uptake was found in high IDH3a expression group. Glucose transporter 1 (GLUT1) level was demonstrated to correlate with IDH3a expression, but not for hexokinase 2 (HK2). Furthermore, A549 and H1299 cells experiment showed, the expression of p‐AKT and GLUT1 were significantly downregulated after IDH3a interference. The cellular uptake of [ 18 F]‐FDG and lactate production were significantly reduced in treatment group. In summary, high expression of IDH3a in lung adenocarcinoma patients is associated with higher glucose uptake. IDH3a targets AKT‐GLUT1 pathway to affect glucose uptake and metabolites in lung adenocarcinoma.

miR–9-5p regulates immunometabolic and epigenetic pathways in β-glucan–trained immunity via IDH3α

“…This indicated that the metabolic and epigenetic changes were intertwined and highly dependent on miR–9-5p expression in trained immunity. Diminished IDH3 activity results in the metabolic switch from oxidative phosphorylation to glycolysis ( 30 ). IDH3α inactivation reduced the ratio of α-KG to fumarate and succinate ( 10 ).…”

Structures of a constitutively active mutant of human IDH3 reveal new insights into the mechanisms of allosteric activation and the catalytic reaction

“…The composing α, β, and γ subunits of HsIDH3 play distinct roles in the assembly, catalytic reaction, and allosteric regulation of the holoenzyme. Mutations and dysregulation of different subunits of HsIDH3 have been associated with various diseases including cancers ( 26 , 27 , 28 ). Therefore, the functional, structural, and mechanistic studies of HsIDH3 have important biological and biomedical significances.…”

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells

“…Curcumin has been previously shown to synergize the augmentation of ROS level by anticancer drugs (47). SDH and IDH3A have been implemented in the regulation of ROS generation in malignant pathologies (48), chemoresistance (49), glucose uptake (50), and invasion (51). Curcumin was able to induce SDH expression and repress the IDH3a in HepG2 cells both in normal or elevated level of glucose.…”