Ras-induced Epigenetic Inactivation of the RRAD (Ras-related Associated with Diabetes) Gene Promotes Glucose Uptake in a Human Ovarian Cancer Model

Abstract

Background: Increased glucose uptake is essential for carcinogenesis. Results: Ras V12 -induced epigenetic inactivation of RRAD promotes glucose uptake and tumor formation. Conclusion: RRAD might act as a functional tumor suppressor by inhibiting glucose uptake. Significance: Down-regulation of RRAD in tumor tissues might be associated with the Warburg effect.

Next generation sequencing of RNA reveals novel targets of resveratrol with possible implications for Canavan disease

“…For example, it up-regulates the expression of E2F1, which besides being important for the regulation of the cell cycle and apoptosis, also regulates metabolism by mediating the switch from the oxidative to the glycolytic pathways [86]. In line with this we show that, RRAD, which is repressed in a number of cancers leading to increased uptake of glucose [71,72,[87][88][89][90], is strongly up-regulated by RSV. We conclude that in cultured human fibroblasts RSV has a SIRT1-independent effect on important factors that affect all pathways influenced by p53, namely cell cycle arrest, DNA repair, apoptosis, and the Warburg effect.…”

“…We confirm transcriptional up-regulation of ACADVL in normal human fibroblasts and we show that RSV also produces a strong up-regulation of RRAD. RRAD is known to inhibit insulinstimulated cellular uptake of glucose and is a direct transcriptional target of p53 [71,72]. RRAD is highly expressed in heart, lung, and skeletal muscle, and it is highly expressed early after skeletal muscle injury and muscle regeneration [73].…”

DNA Damage Response and Autophagy: A Meaningful Partnership

“…Indeed, the autophagy inhibitor chloroquine has been shown to impair DNA damage repair and to increase the cytotoxic effect of the chemotherapeutic agent carboplatin in breast cancer stem cells (Liang et al, 2016). Accumulating evidence indicates that autophagy is exploited by tumor cells to resist radiation or chemotherapy-induced cell death and that genetic or pharmacological inhibition of autophagy sensitizes malignant cells to genotoxic therapy both in vitro and in experimental mouse models (Amaravadi et al, 2007; Pan et al, 2011; Chittaranjan et al, 2014; Wang and Wu, 2014; Filippi-Chiela et al, 2015; Liang et al, 2016; Piya et al, 2016). In line with this is the presence of autophagic vacuoles in Saos2 cells ( Figure 2 ), a p53 null human osteosarcoma cell line, which after prolonged expression of p21 WAF1/Cip1 exhibit enhanced aggressiveness and chemoresistance by deregulating the replication licensing machinery causing replication stress and fuelling genomic instability (Galanos et al, 2016).…”

Brahma-related gene 1 inhibits proliferation and migration of human aortic smooth muscle cells by directly up-regulating Ras-related associated with diabetes in the pathophysiologic processes of aortic dissection

“…Emerging data have illuminated the fact that the potential mechanisms within the tumor suppression functions of RRAD may lie in its negative regulation effect on cell migration and invasion, as well as on the processes of glucose uptake and glycolysis. 19,31,32 FIGURE 5. The RRAD was a crucial mediator for Brg1 in achieving its suppressive effects on proliferation and migration of HASMCs.…”