GEM-based metabolic profiling for Human Bone Osteosarcoma under different glucose and glutamine availability

Abstract

Cancer cell metabolism is dependent on cell-intrinsic factors like genetics, and cell-extrinsic factors like nutrient availability. In this context, understanding how these two aspects interact and how diet influences cellular metabolism is important for developing personalized treatment. In order to achieve this goal, genome-scale metabolic models (GEMs) are used, however, genetics and nutrient availability are rarely considered together. Here, we propose an integrated metabolic profiling, a framework that allows to enrich GEMs with metabolic gene expression data and information about nutrients. First, the RNA-seq is converted into Reaction Activity Score (RAS) to further scale reaction bounds. Second, nutrient availability is converted to Maximal Uptake Rate (MUR) to modify exchange reactions in a GEM. We applied our framework to the human osteosarcoma cell line (U2OS). Osteosarcoma is a common and primary malignant form of bone cancer with poor prognosis, and, as indicated in our study, a glutamine-dependent type of cancer.

Identification and validation of a novel LncRNA TRG-AS1 that inhibits colorectal cancer proliferation and glycolysis

“…Metabolic reprogramming, which is one of the hallmarks of cancer, is one of the key drivers of the cancer initiation and progression [26][27][28]. Reprogramming of cellular metabolism accelerates the rapid proliferation and long-term maintenance of cells [29,30]. LncRNAs are able to regulate complex biological processes via diverse mechanisms, particularly in glycolysis, de novo synthesis of lipids, glutamine and mitochondrial metabolism [31,32].…”