HOTAIR at the metabolic crossroads: lncRNA control of carbohydrate and lipid metabolism

Cancer cells reprogram their metabolic networks to sustain continuous proliferation, resist stress, and support invasive behavior. This metabolic rewiring includes enhanced aerobic glycolysis, increased glutaminolysis to fuel biosynthetic reactions, activation of the pentose phosphate pathway (PPP) for nucleotide synthesis and redox balance, and reorganization of lipid metabolism to integrate membrane biogenesis and energy adaptation. While several oncogenes are well established as metabolic regulators, it is increasingly recognized that non-coding RNAs also contribute to the control of tumor metabolic phenotypes. Among them, the long non-coding RNA (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) has emerged as one of the most consistently upregulated and functionally relevant lncRNAs in human cancers. Accumulating evidence links HOTAIR to metabolic reprogramming in diverse tumor types. HOTAIR controls the expression and activity of key glycolytic enzymes and regulates lipogenesis, lipid accumulation, and metastatic lipid remodeling. However, findings remain dispersed across individual studies, and a consolidated framework integrating HOTAIR regulation with major metabolic pathways is currently lacking. This review synthesizes current knowledge on how HOTAIR drives metabolic rewiring in cancer, with a focus on carbohydrate and lipid metabolism, and discusses the underlying molecular mechanisms and therapeutic implications.