FOXN2 is downregulated in breast cancer and regulates migration, invasion, and epithelial&amp;ndash;mesenchymal transition through regulation of SLUG

Ye, Hui; Duan, Meiling

doi:10.2147/cmar.s176938

Cited by 19 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study is the first to reveal the possible relationship between HOXC6/miR-188-5p and FOXN2 in cell migration. A previous study showed that FOXN2 may be associated with cell cycle regulation, proliferation, and DNA damage response [ 33 ], suggesting that FOXN2 may be associated with the expression of genes related to these pathways. We will be further investigated in the future.…”

Section: Discussionmentioning

confidence: 99%

HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

Jeong

Kim

Ahn

2021

IJMS

View full text Add to dashboard Cite

Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3′-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

Jeong

Kim

Ahn

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…15 FOXN4 is a tumor suppressor in breast cancer through inhibition of slug. 16 Importantly, FOXN4 is a key regulator in a variety of biological processes during development. However, little is known about the function of FOXN4 in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

Duan

2020

OTT

Self Cite

View full text Add to dashboard Cite

Background: Fork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear. Purpose: In this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer. Methods and results: We examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells. Conclusion: The present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53.

show abstract

“…FOXM1 was further shown to be induced by TGFβ in kidney cells undergoing EMT, where it was demonstrated to play a significant role (147). Although the Forkhead box transcription factors as discussed above have been shown to regulate EMT in a positive manner, a few of the members of the family, such as FOXF2, FOXN2 and FOXO3a have been found to act as EMT suppressor (148)(149)(150)(151). FOXF2 has been shown to be a negative regulator of EMT in basal-like breast cancer cells and also in triple negative breast cancer cells.…”

Section: Forkhead Box Family Of Transcriptionmentioning

confidence: 99%

“…Moreover, FOXF2 was shown to recruit nuclear receptor corepressor 1 (NCoR1) and histone deacetylase 3 (HDAC3) to the FOXQ1 promoter to repress its transcription. FOXN2, on the other hand, repressed Slug expression by binding to its promoter directly and thereby inhibiting its transcription (149). FOXO3a, another member of the Forkhead box family, has been reported to play a negative regulatory role during EMT in prostate cancer cells.…”

Section: Forkhead Box Family Of Transcriptionmentioning

confidence: 99%

Epithelial–mesenchymal transition and its transcription factors

et al. 2021

View full text Add to dashboard Cite

Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT transcription factors and discussed their role in the process. We have also tried to focus on their mechanism of action, their inter-dependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type dependent manner.

show abstract

FOXN2 is downregulated in breast cancer and regulates migration, invasion, and epithelial–mesenchymal transition through regulation of SLUG

Cited by 19 publications

References 22 publications

HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

Epithelial–mesenchymal transition and its transcription factors

Contact Info

Product

Resources

About