LncRNA HITT Inhibits Lactate Production by Repressing PKM2 Oligomerization to Reduce Tumor Growth and Macrophage Polarization.

ABSTRACT: Lactic acid acidifies the tumor microenvironment and promotes multiple critical oncogenic processes, including immune evasion. Pyruvate kinase M2 (PKM2) is a dominant form of pyruvate kinase (PK) expressed in cancers that plays essential roles in metabolic reprograming and lactate production, rendering it as an attractive therapeutic target of cancer. However, the mechanism underlying PKM2 regulation remains unclear. Here, we show that long noncoding RNA (lncRNA) HIF-1α inhibitor at transcription level (HITT) inhibits lactate production in a PKM2-dependent manner. Mechanistically, it physically interacts with PKM2 mapped to a region that has been involved in both dimer (less-active) and tetramer (more-active) formation, inhibiting PKM2 oligomerization and leading to dramatic reducti

SUBMITTER: Zhao K 

PROVIDER: S-EPMC9285634 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature