IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment.

ABSTRACT: The acidic microenvironment is considered an important factor in colorectal cancer (CRC) that contributes to malignant transformation. However, the underlying mechanism remains unclear. In a previous study, we confirmed that IDH1 K224 deacetylation promotes enzymatic activity and the production of α-KG. Here, we further investigate the effect of IDH1 hyperacetylation on the CRC acidic microenvironment. We demonstrate that increased α-KG affects hydroxylation of Ago2 and mediates miR-9-5p targeting NHE1 protein. Knockdown of NHE1 dramatically attenuates CRC cell proliferation and migration by restricting transport of intracellular H⁺ out of cells. Furthermore, we show that miR-9-5p is the microRNA with the most significant difference in the alteration of IDH1 K224 acetylation and

SUBMITTER: Wang B 

PROVIDER: S-EPMC10339209 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature