The Wnt/β-catenin-P2-HNF4α feedback loop facilitates colorectal tumorigenesis and malignancy.

ABSTRACT:

Background

The Wnt/β-catenin signaling pathway is a crucial regulator of colorectal cancer (CRC) development; however, its downstream targets and mechanistic contributions to tumorigenesis remain incompletely understood. Hepatocyte nuclear factor 4 alpha (HNF4α), a transcription factor primarily studied in liver function and hepatocarcinogenesis, has an unclear role in CRC. This study investigates the antagonistic and synergistic effects of HNF4α isoforms driven by the P1 and P2 promoters on Wnt/β-catenin signaling in colorectal cancer.

Methods

We assessed P1/P2-HNF4α expression and its regulation by Wnt/β-catenin signaling using bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), in vitro and in vivo CRC models, and clinical tumor samples. Chromatin immun

SUBMITTER: Bai W 

PROVIDER: S-EPMC12625555 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature