The Regulation And Mechanisms Of MiR-200c/141 On Breast Cancer And Breast Cancer Stem Cell Heterogeneity

Cancer has been a worldwide problem,and breast cancer is one of the major threats to women's health.Different subtypes of breast cancer have corresponding treatment methods,but chemotherapeutic drug resistance in the treatment process is getting more and more attention.It is currently believed that chemotherapeutic drugs can kill most tumor cells and enrich a small population of cancer stem cells with self-renewal and differentiation characteristics.If we can do in-depth research on cancer stem cells,and ultimately find drugs targeting cancer stem cells,combined with traditional chemotherapy drugs can play a very good role in the treatment of cancer.Recently,more and more evidence indicates that the status of two breast cancer stem cells with different proliferation and migration ability can be converted,and the heterogeneity of breast cancer stem cells is strictly regulated by intracellular and extracellular molecules,and microRNAs also plays a key regulatory role.MiR-200c/141 is abnormally expressed in many human cancers,suggesting that the expression of miR-200c/141 may affect the progression of cancer.Therefore,to explore the regulation mechanism of miR-200c/141 on breast cancer and breast cancer stem cells may provide a new target for better treatment of breast cancer.The miR-200c/141 cluster is a member of the miR-200 family in the same gene cluster.Previous studies have shown that the miR-200 family affects the invasion and metastasis of breast cancer cells by the transition of epithelial-like cells to mesenchymal-like cells(EMT).However,the impact of the miR-200 family on the proliferation of cancer cells is controversial.Therefore,our current research focuses on the regulation of breast cancer stem cell heterogeneity by miR-200c/141 cluster and its influence on the development of breast tumors.Using a miR-200c/141 conditional knockout mouse model of spontaneous breast tumors,we found that knockout of the miR-200c/141 cluster inhibited tumor growth but significantly promoted lung metastasis in mice.Further experimental results indicate that the miR-200c/141 cluster regulated the tumor cell proliferation and metastasis by directly up-regulating the homologous domain-interacting protein kinase 1(HIPK1).Finally,we found that HIPK1 activates ?-catenin to regulate breast cancer stem cells heterogeneity,promote tumor invasion and inhibit breast cancer cell proliferation to a certain extent.miR-200c/141 or HIPK1 may be a potential target for the treatment of breast cancer.However,miR-200c/141 play a biphasic regulatory role in the development of breast tumors.Therefore,when the treatment of miR-200c/141 is applied to different stages of the disease,the potential therapeutic benefits and adverse side effects must be carefully evaluated in order to achieve a better therapeutic effect.