FOXF2 acts as a crucial molecule in tumours and embryonic development

Abstract

As a key member of the forkhead box transcription factors, forkhead box F2 (FOXF2) serves as a transcriptional regulator and regulates downstream gene expression in embryonic development, metabolism and in some common diseases, such as stroke and gastroparesis. Recent studies have shown that aberrant expression of FOXF2 is associated with a variety of tumorigenic processes, such as proliferation, invasion and metastasis. The role of FOXF2 in the development of many different organs has been confirmed by studies and has been speculated about in case reports. We focus on the mechanisms and signal pathways of tumour development initiated by aberrant expression of FOXF2, and we summarize the diseases and signal pathways caused by aberrant expression of FOXF2 in embryogenesis. This article highlights the differences in the role of FOXF2 in different tumours and demonstrates that multiple factors can regulate FOXF2 levels. In addition, FOXF2 is considered a biomarker for the diagnosis or prognosis of various tumours. Therefore, regulating the level of FOXF2 is an ideal treatment for tumours. FOXF2 could also affect the expression of some organ-specific genes to modulate organogenesis and could serve as a biomarker for specific differentiated cells. Finally, we present prospects for the continued research focus of FOXF2. Facts FOXF2 exhibits inhibitory effects in most tumours. In lung cancer (except for non-small cell lung cancer) and rhabdomyosarcoma in mice, FOXF2 mainly shows a promotive effect. FOXF2 can both inhibit and promote HCC and breast cancer. Regulating the expression level of FOXF2 is an ideal treatment for tumours. Mutations in or deletions of FOXF2 occur in some patients with craniofacial deformities. Mice with suppressed FOXF2 expression show defective organogenesis, such as aglossia, eye deformity, cleft palate and intracranial haemorrhage. Open questions Does FOXF2 have a common mechanism in tumours? What signalling pathways and gene expression does FOXF2 affect in the development of different organs? Are there any specific mechanisms or proteins that can be targeted in the treatment of a FOXF2-affected diseases?

CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis

“…FOXF2 is a transcription factor that is involved in the processes of tumorigenesis and is considered to be a biomarker for tumor diagnosis. 17 For example, FOXF2 hindered Hela cell propagation and metastasis, and might serve as a prognostic biomarker for cervical cancer. 29 FOXF2 was downregulated in HCC and might be a promising target in HCC remedy.…”

“…16 The transcription regulator forkhead box F2 (FOXF2) is a critical molecule that participates in embryogenesis and tumorigenic processes. 17 FOXF2 level was lessened in OSCC tissues and FOXF2 silence signally accelerated OSCC cells progression. 18 However, whether FOXF2 was implicated in miR-454-3p-mediated OSCC progression has not been reported.…”

Cis-Repression of Foxq1 Expression Affects Foxf2-Mediated Gene Expression in Palate Development

“…Potential cis-regulatory effects on neighboring genes should also be taken into consideration when analyzing pathogenicity of human gene deletion variants. In addition, since Foxf2 mutant mouse studies have shown that multiple tissues and developmental processes, including pericyte development and maturation of the blood-brain barrier, development of the respiratory and digestive organs, in addition to craniofacial and palate tissues, depend on Foxf2 function (reviewed by He et al, 2020), the (Foxf2/Foxq1) +/− mice provide a valuable resource for understanding the cross-regulation and combinatorial functions of the Foxf2 and Foxq1 genes in multiple developmental and disease processes.…”

Forkhead box F2 as a novel prognostic biomarker and potential therapeutic target in human cancers prone to bone metastasis: a meta-analysis

“…10 Forkhead box F2 (FOXF2; also known as FKHL6, FREAC-2 and FREAC2) is a member of the FOX transcription factor family, which locates at human chromosome 6p25.3 (Figure 1). 11 It consists of 6028 base pairs and produces a functional protein comprising of 444 amino acids. 11 During embryonic development and tissue differentiation, FOXF2 plays a key role in maintaining tissue homeostasis by promoting mesenchymal cell differentiation and inhibiting mesenchymal transformation of adjacent epithelial cells.…”

“…11 It consists of 6028 base pairs and produces a functional protein comprising of 444 amino acids. 11 During embryonic development and tissue differentiation, FOXF2 plays a key role in maintaining tissue homeostasis by promoting mesenchymal cell differentiation and inhibiting mesenchymal transformation of adjacent epithelial cells. 12 Recent studies have shown that FOXF2 plays a critical role in the development and poor prognosis of several types of cancer prone to bone metastasis, such as breast cancer, oesophageal squamous cell cancer, gastric cancer, hepatocellular cancer, colorectal cancer, nonsmall-cell lung cancer, prostate cancer and renal cell carcinoma.…”