Mir-4319 Suppresses The Malignancy Of Triple-negative Breast Cancer By Regulating Self-renewal And Tumorigenesis Of Stem Cells

Background/Aims High levels of cancer stem cells(CSCs)in patients with triple-negative breast cancer(TNBC)correlate with risk of poor clinical outcome and possibly contribute to chemoresistance and metastasis in patients with highly malignant TNBC.Aberrant micro RNA expression is associated with the dysfunction of self-renewal and proliferation in cancer stem cells,while there is little information about the TNBC-specific micro RNAs in regulating CSC ability.Methods Solexa deep sequencing was performed to detect the expression levels of TNBC or non-TNBC stem cells(CSCs)micro RNAs.Mammosphere formation assay,q RT-PCR and the xenograft model in nude mice were performed.Bioinformatic analysis and microarray were used to select the target gene,and luciferase reporter assays were used to confirm the binding sites.Results Solexa sequencing data exhibited differential expression of 193 micro RNAs between TNBC and non-TNBC stem cells.The gene ontology analysis and pathways analyses showed that genes were involved in the maintenance of stemness.Mir-4319 could suppress the self-renewal and formation of tumorspheres in TNBC CSCs through E2F2,and also inhibited tumor initiation and metastasis in vivo.Moreover,increased E2F2 could reverse the effect of mir-4319 on the self-renewal in TNBC CSCs.Conclusions Mir-4319 suppresses the malignancy of TNBC by regulating self-renewal and tumorigenesis of stem cells and might be a remarkable prognostic factor or therapeutic target for patients with TNBC.