The Mechaoism Of CDCA5 Regulating On Tri-negative Breast Cancer Proliferation And Metastasis

Cancer has the unique biological characteristics such as cell differentiation and Abnormal proliferation,infiltration and metastasis,and its occurrence is a complex result of multiple risk factors.According to the WHO,only in 2017,there were about 14 million new cases of cancer and 8.8 million deaths for cancer.Cancer has become the second leading cause of death worldwide.As a kind of gland malignant tumors which happened in mammary epithelial cell,breast cancer has become the first incidence of female cancer worldwide.About 30% of new female cancer cases were breast cancer and 14% of all female cancer deaths were coursed by breast cancer.It has been a serious threat to women's health.Among them,triple-negative breast cancer accounts for about 20% of breast cancer,which is a kind of breast cancer with higher degree of malignancy and invasion.Compared to other kinds of breast cancer,the tri-negative breast cancer is lack of Estrogen receptor(ER)and Progesterone receptor(PR)and Human epidermal growth factor receptor 2(HER2)expression and lack of effective treatment,and results faster disease process in patients,who got a higher mortality rate and metastasis rate in five years.Currently,the main therapeutic methods such as surgery,chemoradiotherapy,endocrine therapy,and immunotherapy,have poor effect on the treatment of triple-negative breast cancer.Therefore,it is a great significance to explore new therapeutic targets for triple-negative breast cancer.Our laboratory is devoted to the regulation of the occurrence,development,metastasis of protein and its mechanism in triple-negative breast cancer.We used bioinformatics technology to analyze a series protein which get higher expression in tri-negative breast cancer tissues than adjacent tissues and the clinical correlation analysis of these proteins in multiple cancer related database such as TCGA,METABRIC.Compared with the normal breast tissue,the cell division cycle associated 5(CDCA5)is significantly higher expression in the triple-negative breast cancer breast cancer,and its expression level is negatively correlated with the prognosis of patients with breast cancer.And CDCA5 has not previously been reported in breast cancer.Therefore,we listed CDCA5 as the target of further studies and explored its function and mechanism in the occurrence and development of the triple-negative breast cancer.First of all,we stained human breast cancer tissue microarray with immunohistochemical technique,and scored the expression of CDCA5,and found that the expression of CDCA5 in tri-negative breast cancer tissue was higher than that in normal breast cancer tissue;The prognostic correlation analysis of patients with high expression of CDCA5 showed that the prognosis of patients with high expression of CDCA5 was poor and the probability of occurrence and metastasis was higher.It suggested that CDCA5 plays a key role in the occurrence and development of tri-negative breast cancer.Next,we detected the CDCA5 protein expression level in breast cancer cell lines by Western Blot,found that it's high expression in triple-negative breast cancer cell lines,suggesting that CDCA5 may be an important protein in triple-negative breast cancer cells.Subsequently,we successfully used lenti-virus infection system and shRNA interference technique to stably knock down the expression of CDCA5 gene in triple-negative breast cancer cell lines,which provided effective tools for further functional study and mechanism study.In the assay of cell viability,we found that knocking down CDCA5 could effectively inhibit the proliferation of tri-negative breast cancer cell lines.And the transwell experiment shows that knock down CDCA5 can significantly inhibit the invasion ability of the triple-negative breast cancer cell lines.The results of the xenografts nude mice model showed that the tumorigenesis of tri-negative breast cancer cells in the intervention group was poor in mice,which indicated that interference CDCA5 could significantly inhibit the occurrence and growth of triple negative breast cancer.The above results suggested that CDCA5 plays a significant role in the tumorigenesis,development and metastasis of triple-negative breast cancer.Flow cytometry was used to detect the cycle of tri-negative breast cancer cells in interference group and control group.We found that knocking down CDCA5 could block tri-negative breast cancer cells from S phase.It is suggested that CDCA5 may influence the process of tumorigenesis,development and metastasis by regulating cell cycle progression in tri-negative breast cancer cells.In conclusion,this study first revealed the high expression of CDCA5 in breast cancer and negative correlation with prognosis;Secondly,CDCA5 plays a vital role in the tumorigenesis,development and metastasis of tri-negative breast cancer cells.Finally,it is preliminarily clarified that CDCA5 plays its role by regulating the cell cycle process.In the future research,we will further study the effect of CDCA5 on the cell cycle of tri-negative breast cancer cells,reveal the regulatory function and related mechanisms of CDCA5 on tri-negative breast cancer cells.And we hope that it can provide scientific basis and innovative ideas for clinical treatment of tri-negative breast cancer.