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Published on: August 23, 2019

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression

Tian Zhou^1,2, Ning Ma^1,3, Yong-Lin Zhang²

¹School of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, Guizhou, China.

|January 31, 2024

Abstract

Objective:

In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer.

Methods:

FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model.

Results:

Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors.

Conclusion:

The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells.

Insights

Elevated FOXP4 levels drive thyroid cancer (TC) progression by suppressing FBXW7. Restoring FBXW7 expression inhibits TC cell growth and malignant phenotypes, offering a potential therapeutic target for this rising cancer.

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

Thyroid cancer (TC) incidence is increasing globally.
FOXP4, a transcription factor, is implicated in various cancers but its role in TC is unclear.
Understanding FOXP4's function in TC is crucial for developing targeted therapies.

Purpose of the Study:

To investigate the role of transcription factor FOXP4 in thyroid cancer.
To elucidate the functional relationship between FOXP4 and its target gene FBXW7 in TC.
To determine the impact of FOXP4 and FBXW7 on TC cell behavior and tumor growth.

Main Methods:

Assessed FOXP4 and FBXW7 expression in TC tissues and cell lines using immunohistochemistry and RT-qPCR.
Investigated FOXP4's effects on cell proliferation, migration, cell cycle, and epithelial-mesenchymal transition (EMT).
Confirmed FOXP4-FBXW7 interaction via ChIP assays and evaluated FBXW7's impact on FOXP4-driven phenotypes in vitro and in vivo.

Main Results:

Higher FOXP4 levels and lower FBXW7 levels correlated with aggressive papillary thyroid carcinoma.
FOXP4 overexpression promoted TC cell proliferation, migration, and EMT.
FOXP4 directly suppressed FBXW7 transcription; FBXW7 restoration counteracted FOXP4's effects.
FOXP4 knockdown reduced tumor growth and increased FBXW7 levels in vivo.

Conclusions:

FOXP4 acts as a key regulator of FBXW7 transcription in thyroid cancer.
Aberrant FBXW7 expression driven by FOXP4 contributes to malignant phenotypes in aggressive TC.
Targeting the FOXP4-FBXW7 axis may offer a novel therapeutic strategy for thyroid cancer.

Read full analysis

Keywords:

EMT FBXW7 FOXP4 Thyroid cancer Tumor transplant

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