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

• Published in: Analytical cellular pathology (Amsterdam) 2022-10, Vol.2022, p.1-13
• Main Authors: Zhao, Jinlai, Wang, Yigang, Wang, Yang, Gao, Jianchao, Yang, Haichao, Wu, Xiaotang, Li, Hua
• Format: Article
• Language: English
• ISSN: 2210-7177; 2210-7185
• DOI: 10.1155/2022/8275574

Background. Colon cancer is a common gastrointestinal malignancy. It has been discovered that Farnesoid X receptor (FXR) plays an imperative regulatory role in multitype cancers in recent years. However, its regulatory mechanism in colon cancer has not been clearly explored. This study intended to explore the molecular regulatory mechanism of FXR and its downstream genes on the malignant progression of colon cancer. Methods. The mRNA and protein expression of FXR in colon cancer cells were measured by quantitative real-time polymerase chain reaction and Western blot. The effects of FXR on the biological function of colon cancer cells were measured by Cell Counting Kit-8, colony formation, and transwell assays. The downstream target gene of FXR was predicted by bioinformatics analysis and found to be associated with cellular oxidative phosphorylation. The binding relationship between FXR and its downstream gene dehydrogenase/reductase member 9 (DHRS9) was verified through luciferase reporter assay and chromatin immunoprecipitation assay. The changes of oxidative phosphorylation were detected by Western blot and oxygen consumption rate determination. The effect of FXR/DHRS9 axis on the malignant progression of colon cancer cells was further confirmed by rescue experiments. Results. FXR was underexpressed in colon cancer tissues and cells, and overexpressing FXR could repress the malignant behaviors of colon cancer cells. Besides, DHRS9 was a downstream gene of FXR, and FXR/DHRS9 inhibited the deterioration of colon cancer through inhibiting oxidative phosphorylation. Moreover, promoting FXR expression in colon cancer cells could partially reverse the biological function changes caused by silencing DHRS9 expression. Conclusion. FXR inhibited the oxidative phosphorylation and inhibited the malignant progression of colon cancer cells via targeting DHRS9.