Figure 9.

HITT-regulated PKM2-lactate repression inhibits tumor growth in vivo. Pyruvate kinase M2 (PKM2) plays essential roles in metabolic reprograming and lactate production. The tetramer formation of PKM2 has more active PK activity and regulates M2 polarization of macrophages via lactate derived from tumor cells. Under glucose starvation, miR-106 is increased, which inhibits lncRNA HITT levels and facilitates PKM activation and adaptive survival. This is because HITT inhibits PKM2 dimer and tetramer formation and subsequent lactate production into the environment via direct interaction. So HITT inhibits tumor growth by inhibiting PKM2 activity and promoting macrophage polarization to M1.