The Study On The Regulation Of Breast Cancer Stem Cells By Transcription Factor FOXA2

Mammary gland tumors are the most common tumor types in female gynecologic tumors.According to a global cancer report issued by the World Health Organization,the number of newly-increased breast cancer patients in the world is about 1.671 million,and about 522,000 people die each year.The numerous subtypes and high heterogeneity of breast tumors make breast cancer diagnosis more difficult.Among them,triple-negative subtypes of breast cancer have high invasiveness and recurrence,leading to worse prognosis and shorter survival time.Cancer Stem Cells(CSCs)are a special subpopulation of tumors that account for a very small proportion of tumors.Studies have shown that cancer stem cells have the ability to self-renew,have important functions in maintaining the proliferation and differentiation of tumor cell populations,and have anti-apoptotic and damage escape capabilities when the tumor cell population is subjected to exogenous damage.FOXA2 is a member of the FOX transcription factor family.Early research on FOXA2 found that it has important pro-differentiation functions in embryonic development.The homozygous deletion of Foxa2 in mouse embryos will directly lead to embryonic lethality.Follow-up studies have shown that FOXA2 acts as a tumor suppressor and can inhibit the proliferation of many tumors such as lung cancer,liver cancer,gastric cancer,breast cancer,and lung squamous cell carcinoma.In this paper,the function of transcription factor FOXA2 in breast tumors was studied.Combined with comprehensive analysis of clinical patient tumor database,it was found that patients with high expression of FOXA2 in triple negative breast cancer showed lower survival rate and survival time.In the triple-negative breast cancer cell model MDA-MB-231,knockdown of FOXA2 expression led to a significant decrease in tumor cell pluripotency markers with the CRISPR/Cas9 gene editing tool.The results of microsphere culture experiments showed that the ability to knock down FOXA2 in MDA-MB-231 cells significantly decreased.Using the MDA-MB-231 cell line to establish a Tex-mediated Tet-ON FOXA2-induced cell model,after induction of FOXA2 upregulation,the cell stem markers were significantly up-regulated,and their ability to form the ball was significantly enhanced.Dual-luciferase reporter assays were used to demonstrate that FOXA2 activates the promoters of the genes important for stem cell-associated genes ALDHA1,ALDHA2,and OCT4.The above results indicate that FOXA2 has an important role in maintaining the dryness of triple negative breast cancer tumor cells.