PurposeIncreasing evidence indicates that members of forkhead transcription factor family (FOXO) play key roles in cell proliferation and apoptosis in multiple cancers, including prostate cancer. However, the underlying mechanism of FOXO6 was not yet known. The aim of our work is to investigate the function of FOXO6 in breast cancer.MethodsIn the present study, quantitative real-time polymerase chain reaction and Western blotting analyses were used to detect the expression of FOXO6 in breast cancer tissues and cell lines.ResultsThe results revealed that FOXO6 was downregulated in breast cancer tissues and cell lines, compared with adjacent normal tissues and MCF-10A cells, respectively. Moreover, the expression of FOXO6 was associated with the expression of epithelial–mesenchymal transition (EMT) indicator proteins, such as E-cadherin and N-cadherin. Additionally, our findings suggested that FOXO6 expression was negatively associated with tumor size (p=0.002), pathological grade (p=0.018) and lymph node metastasis (p=0.003). Sirt6 has been found to promote cell proliferation and metastasis in several cancers, and quantitative chromatin immunoprecipitation and luciferase reporter assays indicated FOXO6 transcriptionally regulated Sirt6 expression. Furthermore, various functional experiments, including wound healing assay, transwell invasion assay, colony formation assay and Cell Counting Kit-8 assay, revealed that FOXO6 suppressed cell migration, invasion, and proliferation of breast cancer cells.ConclusionIn conclusion, FOXO6 serves as a tumor suppressor in breast cancer, and suppresses EMT through regulation of Sirt6.
IntroductionForkhead box (FOX) N2 (FOXN2), a member of FOX protein family, has been reported to play critical roles in some types of cancers. However, the expression and function of FOXN2 in breast cancer remain unclear.MethodsIn the present work, we explored the detailed molecular mechanism of FOXN2 in breast cancer. We performed RT-qPCR and Western blotting analysis to detect the expression of FOXN2 in breast cancer. Colony formation assay, CCK-8 assay, wound healing assay, and Transwell assay were used to determine the effect of FOXN2 on cell proliferation, migration, and invasion in breast cancer.ResultsOur results demonstrated that FOXN2 was downregulated in breast cancer tissues and cell lines. Downregulation of FOXN2 was correlated with tumor size, pathological grade, and lymph node metastasis. The in vitro experiments revealed that the ectopic expression of FOXN2 significantly suppressed the proliferation, migration, and invasiveness of breast cancer cells, and inhibition of FOXN2 promoted the proliferation, migration, and invasiveness of breast cancer cells. Moreover, inhibition of FOXN2 facilitated epithelial–mesenchymal transition (EMT) through regulation of SLUG.ConclusionTaken together, our results showed for the first time that FOXN2 plays an essential role in cell proliferation and invasion. Thus, FOXN2 may be an attractive therapeutic target for the treatment of breast cancer.
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.
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