Figure 3.

Mitochondrial and lipid metabolism are profoundly influenced by non-coding RNAs in cancer cells. The accelerated energetic demand of cancer cells is regulated by the mitochondrial enzyme glutaminase (GLS), a crucial molecular switch whose activity is finely regulated by nRNAs; miR-192 and miR-204, as an example, enhance the production of GLS via down-regulation of the HOTTIP lncRNA. c-Myc positively regulates glutamine metabolism by enhancing the expression of GLS through the suppression of miR-23A/B and/or down-regulation of GLS-AS (nuclear-located antisense lncRNA of glutaminase), which post-transcriptionally inhibits the expression of GLS. GLS-AS, in turn, can decrease c-Myc expression, thus creating a reciprocal feedback loop regulated by glutamine deprivation. Lipid metabolism is regulated by several ncRNAs; miR-185 and miR-342 regulate the activity of SREBP1 (sterol regulatory element binding protein), a master regulator of cholesterol synthesis and lipid utilization, whose target genes include, among others, FASN (fatty acid synthase) and HMGCR (3-hydroxy-3-methyl-glutaryl CoA reductase). lncRNAs implicated in lipid metabolism of cancer cells include, among others, SPRY4-IT1, LSTR, and SRA, the latter inducing adipogenesis through the activation of PPAR-gamma. Red arrows indicate a positive regulation, while truncated red arrows indicate inhibitory mechanisms.