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Transcription Factor FXR Activates DHRS9 to Inhibit the Cell Oxidative Phosphorylation and Suppress Colon Cancer

Jinlai Zhao1, Yigang Wang2, Yang Wang1

  • 1Gastrointestinal surgery, Tangshan Central Hospital, Tangshan, Hebei 063000, China.

Analytical Cellular Pathology (Amsterdam)
|November 7, 2022
PubMed
Abstract

Insights

Farnesoid X receptor (FXR) is underexpressed in colon cancer. Upregulating FXR and its target gene DHRS9 inhibits colon cancer progression by suppressing oxidative phosphorylation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Colon cancer is a prevalent gastrointestinal malignancy.
  • Farnesoid X receptor (FXR) is increasingly recognized for its regulatory role in various cancers.
  • The specific mechanisms of FXR in colon cancer remain underexplored.

Purpose of the Study:

  • To elucidate the molecular regulatory mechanism of FXR and its downstream targets in colon cancer progression.
  • To investigate the role of the FXR/DHRS9 axis in colon cancer pathogenesis.
  • To determine the impact of FXR on cellular oxidative phosphorylation in colon cancer.

Main Methods:

  • Quantitative real-time PCR and Western blot to assess FXR expression.
  • Cell Counting Kit-8, colony formation, and Transwell assays to evaluate cellular functions.
  • Bioinformatics, luciferase reporter assays, and ChIP assays to identify and validate FXR's downstream target DHRS9.
  • Oxygen consumption rate determination to measure oxidative phosphorylation.

Main Results:

  • FXR expression was found to be downregulated in colon cancer tissues and cells.
  • Overexpression of FXR suppressed malignant behaviors of colon cancer cells.
  • DHRS9 was identified as a downstream target of FXR, and the FXR/DHRS9 axis inhibited colon cancer progression by suppressing oxidative phosphorylation.
  • Restoring FXR expression partially reversed biological function changes induced by DHRS9 silencing.

Conclusions:

  • FXR inhibits colon cancer cell progression by targeting DHRS9 and suppressing oxidative phosphorylation.
  • The FXR/DHRS9 pathway represents a potential therapeutic target for colon cancer treatment.

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