A Point Mutation R122C in RUNX3 Promotes the Expansion of Isthmus Stem Cells and Inhibits Their Differentiation in the Stomach.

ABSTRACT:

Background & aims

RUNX transcription factors play pivotal roles in embryonic development and neoplasia. We previously identified the single missense mutation R122C in RUNX3 from human gastric cancer. However, how RUNX3^R122C mutation disrupts stem cell homeostasis and promotes gastric carcinogenesis remained unclear.

Methods

To understand the oncogenic nature of this mutation in vivo, we generated the RUNX3^R122C knock-in mice. Stomach tissues were harvested, followed by histologic and immunofluorescence staining, organoid culture, flow cytometry to isolate gastric corpus isthmus and nonisthmus epithelial cells, and RNA extraction for transcriptomic analysis.

Results

The corpus tissue of RUNX3^R122C/R122C homozygous mice showed a precance

SUBMITTER: Douchi D 

PROVIDER: S-EPMC8933847 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature