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. 2022 May;49(5):3617-3625.
doi: 10.1007/s11033-022-07201-x. Epub 2022 Mar 28.

Farnesoid X receptor functions in cervical cancer via the p14ARF-mouse double minute 2-p53 pathway

Xiaohua Huang  1 , Bin Wang  2 , Huimin Shen  3 , Danmei Huang  2 , Ganggang Shi  2
Affiliations

Farnesoid X receptor functions in cervical cancer via the p14ARF-mouse double minute 2-p53 pathway

Xiaohua Huang et al. Mol Biol Rep. 2022 May.

Abstract

Background: Cervical cancer is the second most common cancer among women living in developing countries. Farnesoid X receptor (FXR) is a member of the nuclear receptor family, which regulates the development and proliferation of cancer. However, the role of and molecular mechanism by which FXR acts in cervical cancer are still unknown.

Methods and results: The relationship between FXR and the proliferation of cervical cancer cell lines was detected by MTT and colony formation assays. Immunohistochemistry was used to detect the expression of FXR in cervical cancer tissue slides. Western blotting was used to detect the expression of p14ARF, mouse double minute 2 (MDM2) and p53 when FXR was overexpressed or siRNA was applied. Western blotting was used to detect the expression of MDM2 and p53 when pifithrin-α (PFT-α) was applied. FXR activation inhibited the proliferation of cervical cancer cell lines. FXR was significantly decreased in cervical squamous cell carcinoma, which was correlated with TNM stage, but not with metastasis. Overexpression of FXR activated the p14ARF-MDM2-p53 pathway. As a p53 inhibitor, PFT-α increased MDM2 in Lenti-vector cells, but had no effect on MDM2 in Lenti-FXR cells.

Conclusions: FXR inhibits cervical cancer by upregulating the p14ARF-MDM2-p53 pathway. Activation of FXR may be a potential strategy for the treatment of cervical cancer.

Keywords: Cervical cancer; FXR; MDM2; p14ARF; p53.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
FXR inhibits the proliferation of cervical cancer cell lines
Fig. 2
Fig. 2
Expression of FXR in cervical cancer tissues
Fig. 3
Fig. 3
FXR upregulates the p14ARF-MDM2-p53 pathway in cervical cancer cell lines
Fig. 4
Fig. 4
Protein levels of MDM2 in cervical cancer cells with or without PFT-α treatment
Fig. 5
Fig. 5
The mechanism of FXR-mediated the p14ARF-MDM2-p53 pathway
See this image and copyright information in PMC

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