The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

Abstract

Metabolic reprogramming and elevated glycolysis levels are associated with tumor progression. However, despite cancer cells selectively inhibiting or expressing certain metabolic enzymes, it is unclear whether differences in gene profiles influence patient outcomes. Therefore, identifying the differences in enzyme action may facilitate discovery of gene ontology variations to characterize tumors. Fructose-1,6-bisphosphate (F-1,6-BP) is an important intermediate in glucose metabolism, particularly in cancer. Gluconeogenesis and glycolysis require fructose-1,6-bisphosphonates 1 (FBP1) and fructose-bisphosphate aldolase A (ALDOA), which participate in F-1,6-BP conversion. Increased expression of ALDOA and decreased expression of FBP1 are associated with the progression of various forms of cancer in humans. However, the exact molecular mechanism by which ALDOA and FBP1 are involved in the switching of F-1,6-BP is not yet known. As a result of their pancancer pattern, the relationship between ALDOA and FBP1 in patient prognosis is reversed, particularly in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC). Using The Cancer Genome Atlas (TCGA), we observed that FBP1 expression was low in patients with LUAD and LIHC tumors, which was distinct from ALDOA. A similar trend was observed in the analysis of Cancer Cell Line Encyclopedia (CCLE) datasets. By dissecting downstream networks and possible upstream regulators, using ALDOA and FBP1 as the core, we identified common signatures and interaction events regulated by ALDOA and FBP1. Notably, the identified effectors dominated by ALDOA or FBP1 were distributed in opposite patterns and can be considered independent prognostic indicators for patients with LUAD and LIHC. Therefore, uncovering the effectors between ALDOA and FBP1 will lead to novel therapeutic strategies for cancer patients.

Comprehensive bioinformatics analysis to identify a novel cuproptosis-related prognostic signature and its ceRNA regulatory axis and candidate traditional Chinese medicine active ingredients in lung adenocarcinoma

“…In addition, studies have found that increased metabolic reprogramming and glycolysis levels are associated with tumor progression ( Li et al, 2022 ). Recent studies have shown that glycolysis/gluconeogenesis and carbon metabolism have been proven to be involved in the occurrence and development of lung cancer cells ( He et al, 2022 ; Li et al, 2022 ).…”

“…In addition, studies have found that increased metabolic reprogramming and glycolysis levels are associated with tumor progression ( Li et al, 2022 ). Recent studies have shown that glycolysis/gluconeogenesis and carbon metabolism have been proven to be involved in the occurrence and development of lung cancer cells ( He et al, 2022 ; Li et al, 2022 ). The tumor metabolic microenvironment plays an important role in tumor occurrence, development, invasion, and metastasis ( García-Cañaveras et al, 2019 ; Dey et al, 2021 ).…”

Comparative Transcriptome Analysis of Organ-Specific Adaptive Responses to Hypoxia Provides Insights to Human Diseases

“…Recent studies have demonstrated that the key enzyme ALDOA (aldolase A) in glycolysis is a cancer-related gene according to the Human Protein Atlas information [ 30 ]. HIF1A was also reported to upregulate ALDOA expressions under hypoxic conditions [ 31 ]. HIF has also been shown to enhance the glucose flux in glycolysis in cancer cells to enhance energy usage [ 32 ].…”

Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells

“…ALDOA also has non-enzymatic functions in invasive potential, drug resistance, and stem cell function of cancer cells [ 66 , 67 , 68 ]. It has been suggested that the activities of FBP1 and ALDOA are regulated by endogenous proteins during the FBP conversion [ 69 ].…”