Novel mechanistic targets of forkhead box Q1 transcription factor in human breast cancer cells

Kim, Su‐Hyeong; Hahm, Eun‐Ryeong; Singh, Krishna B.; Singh, Shivendra V.

doi:10.1002/mc.23241

Cited by 8 publications

(12 citation statements)

References 49 publications

(108 reference statements)

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“…The study found that FOXQ1 is a direct transcriptional regulator of IL-1α, IL-8 and vascular endothelial growth factor in breast cancer cells (45). FOXQ1 is upregulated in breast cancer tissues, which promotes EMT, cell migration and invasion, self-renewal and metastasis of breast cancer stem cells (46).…”

Section: Discussionmentioning

confidence: 99%

The Role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer

Hui

et al. 2023

Preprint

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Background Breast cancer is a common malignancy with the highest mortality rate among women worldwide. The Forkhead Box (FOX) transcription factor family is an evolutionarily conserved superfamily that regulates cell growth, differentiation, and tissue development. Increasing evidence suggests that FOX transcription factors play an important role in the occurrence and development of breast cancer. However, little is known about the relationship between the expression, prognostic value, function and immune infiltration of FOX transcription factors in tumor microenvironment.Methods In this research, we studied the expression, prognostic value, gene alteration, functional enrichment and immune cell infiltration of FOX factor in breast cancer patients by using the Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, String, GeneMANIA, DAVID, TIMER, Cytoscape(version3.9.1)and R software (version 3.6.3).Results The expression levels of FOXA1 and FOXM1 were significantly higher in breast cancer tissues than in normal tissues, while the expression levels of FOXC2 and FOXO3 were lower in breast cancer tissues than in normal tissues. The high expression of mRNA in FOXA1, FOXM1 and FOXP1 groups was related to tumor stage. Survival analysis results showed that increased FOXP1 mRNA levels were significantly associated with overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in all breast cancer patients (p < 0.05). Patients with the FOXA1 high-expression group had better RFS and DMFS than the low-expression group (p < 0.05), while patients with FOXM1 high-expression group had worse RFS, OS and DMFS than the low-expression group (p < 0.05). FOXP1, FOXA1 and FOXM1 can be used as potential biomarkers to predict the prognosis of breast cancer patients. Functional enrichment indicated that FOX was mainly involved in cell division, cell senescence, cell cycle and prolactin signaling pathway. In addition, FOX mRNA expression was strongly associated with the infiltration of multiple immune cells, including six types of B cells, CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells in breast cancer.Conclusion These findings may provide novel insights into the screening of prognostic biomarkers of the FOX family in breast cancer, and lays a foundation for further research on the immune infiltration of the FOX transcription factor family members in tumors.

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Section: Discussionmentioning

confidence: 99%

The Role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer

Hui

et al. 2023

Preprint

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“…The RNA‐seq data presented in this study were from our previously published study 14 . The RNA‐seq data was submitted to the Gene Expression Omnibus of NCBI (GSE151059) 14 …”

Section: Methodsmentioning

confidence: 99%

“…The forkhead Box Q1 (FoxQ1) is another transcription factor implicated in the pathogenesis of breast cancer. Overexpression of FoxQ1 has been reported in basal‐like and luminal‐type human breast cancers when compared to normal mammary tissue 13,14 . In breast cancer, the FoxQ1 is best known for its role in promotion of epithelial to mesenchymal transition (EMT) and maintenance of breast cancer stem‐like cells (bCSC) 15–17 .…”

Section: Introductionmentioning

confidence: 99%

“…Initial studies showed that FoxQ1 is a transcriptional repressor of E‐cadherin that explains the EMT promotion by FoxQ1 15 . Recently, we performed RNA sequencing (RNA‐seq) analysis using empty vector transfected and FoxQ1 overexpressing SUM159 cells to identify novel targets of FoxQ1 14 . Overexpression of FoxQ1 resulted in downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis 14 .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we performed RNA sequencing (RNA‐seq) analysis using empty vector transfected and FoxQ1 overexpressing SUM159 cells to identify novel targets of FoxQ1 14 . Overexpression of FoxQ1 resulted in downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis 14 . Overexpression of FoxQ1 resulted in mitotic arrest in SUM159 cells but not in MCF‐7 cells 14 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Kim

Hahm

Singh

2023

Molecular Carcinogenesis

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Forkhead Box Q1 (FoxQ1) transcription factor is overexpressed in luminal‐type and basal‐type human breast cancers when compared to normal mammary tissue. This transcription factor is best known for its role in promotion of breast cancer stem‐like cells and epithelial to mesenchymal transition. The present study documents a novel function of FoxQ1 in breast cancer cells. Overexpression of FoxQ1 in basal‐like SUM159 cells and luminal‐type MCF‐7 cells resulted in increased conversion of microtubule‐associated protein light chain 3 beta‐I (LC3B‐I) to LC3B‐II, which is a hallmark of autophagy. Autophagy induction by FoxQ1 overexpression was confirmed by visualization of LC3B puncta as well as by transmission electron microscopy. Expression profiling for genes implicated in autophagy regulation revealed upregulation of many genes, including ATG4B, ATG16L1, CTSS, CXCR4 and so forth but downregulation of BCL2L1, DRAM1, TNF, ULK2 and so forth by FoxQ1 overexpression in SUM159 cells. Western blot analysis confirmed upregulation of ATG4B and CXCR4 proteins by FoxQ1 overexpression in both SUM159 and MCF‐7 cells. Chromatin immunoprecipitation assay revealed recruitment of FoxQ1 at the promoter of ATG4B. Pharmacological inhibition of ATG4B using S130 significantly increased apoptosis induction by DOX in empty vector transfected as well as FoxQ1 overexpressing SUM159 and MCF‐7 cells but this effect was statistically significantly lowered by FoxQ1 overexpression indicating the protective role of FoxQ1 on apoptosis. Treatment of SUM159 cells with S130 and DOX enhanced LC3B‐II level in both empty vector transfected cells and FoxQ1 overexpressing SUM159 cells but not in FoxQ1 overexpressing MCF‐7 cells. In conclusion, FoxQ1 is a novel regulator of autophagy.

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The FoxQ1 transcription factor is a novel regulator of electron transport chain complex I subunits in human breast cancer cells

Kim

Singh

2021

Molecular Carcinogenesis

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The FoxQ1 is an oncogenic transcription factor that is overexpressed in basal-like and luminal-type human breast cancers when compared to the normal mammary tissue. The FoxQ1 is implicated in mammary tumor progression. However, the mechanism by which FoxQ1 promotes mammary tumorigenesis is not fully understood. In this study, we present experimental evidence for a novel function of FoxQ1 in the regulation of complex I activity of the electron transport chain. The RNA-seq data from FoxQ1 overexpressing basal-like SUM159 cells revealed a statistically significant increase in the expression of complex I subunits NDUFS1 and NDUFS2 when compared to the empty vector (EV) transfected control cells.Consistent with these results, the basal and ATP-linked oxygen consumption rates were significantly increased by FoxQ1 overexpression in SUM159 and luminal-type MCF-7 cells. The FoxQ1 overexpression in both cell lines resulted in increased intracellular levels of pyruvate, lactate, and ATP that was associated with overexpression of pyruvate dehydrogenase and pyruvate carboxylase proteins. Activity and assembly of complex I were significantly enhanced by FoxQ1 overexpression in SUM159 and MCF-7 cells that correlated with increased mRNA and/or protein levels of complex I subunits NDUFS1, NDUFS2, NDUFV1, and NDUFV2. The chromatin immunoprecipitation assay revealed the recruitment of FoxQ1 at the promoters of both NDUFS1 and NDUFV1. The cell proliferation of SUM159 and MCF-7 cells was increased significantly by overexpression of NDUFS1 as well as NDUFV1 proteins. In conclusion, we propose that increased complex I-linked oxidative phosphorylation is partly responsible for oncogenic role of FoxQ1 at least in human breast cancer cells.

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Novel mechanistic targets of forkhead box Q1 transcription factor in human breast cancer cells

Cited by 8 publications

References 49 publications

The Role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer

The Role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer

Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

The FoxQ1 transcription factor is a novel regulator of electron transport chain complex I subunits in human breast cancer cells

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