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

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

  • iScience. 2023 Jun 25;26(7):107206. doi: 10.1016/j.isci.2023.107206.
Bo Wang 1,  Long Zhao 1,  Changjiang Yang 1,  Yilin Lin 1,  Shan Wang 1,  Yingjiang Ye 1,  Jianyuan Luo 2,  Zhanlong Shen 1
Affiliations

Affiliations

  • 1 Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. China.
  • 2 Department of Medical Genetics, Peking University Health Science Center, Beijing 100191, P.R. China.
PMID: 37456829 DOI: 10.1016/j.isci.2023.107206
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 can downregulate NHE1 mRNA. Our data also indicate that hydroxylation stabilizes Ago2, which in turn promotes miR-9-5p activity. Taken together, our results reveal a novel mechanism through which IDH1 deacetylation regulates the cellular acidic microenvironment and inhibits CRC metastasis.

Keywords

Cancer; Cell biology.

Figures
Products