MiR-1976 knockdown promotes epithelial-mesenchymal transition and cancer stem cell properties inducing triple-negative breast cancer metastasis
- Cell Death Dis. 2020 Jul 3;11(7):500. doi: 10.1038/s41419-020-2711-x.
- 1. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
- 2. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
- 3. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. [email protected].
- 4. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
- 5. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. [email protected].
- 6. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
- 7. Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. [email protected].
- 8. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
- # Contributed equally.
Triple-negative breast Cancer (TNBC), characterized by high aggression and invasiveness, has a worse prognosis than Other subtypes of breast Cancer. Establishing a novel animal model is helpful to understand the mechanisms involved in the progress of TNBC metastasis. In a self-established mouse model consisting normal human breast tissues and normal human bone tissues, TNBC cell line SUM-1315 could spontaneously form species-specific bone metastasis. The expression level of miR-1976 in SUM-1315-bo (derived from metastatic bone tumor) was found lower than that in SUM-1315-br (derived from orthotopic breast tumor). MiR-1976 was found to be downregulated in TNBC tissues, and lower expression of miR-1976 was correlated with worse overall survival in a patient cohort obtained from TCGA database. MiR-1976 knockdown promoted epithelial-mesenchymal transition (EMT) and Cancer stem cell (CSC) properties in vitro and in vivo. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) was verified as a target gene by Sequencing, biotinylated miRNA pull-down, and luciferase reporter assay. Moreover, overexpression and suppression analysis implicated PIK3CG as a mediator of the biological effects of miR-1976. Our study demonstrated that miR-1976 knockdown could promote EMT and CSCs by PIK3CG. These findings may reveal mechanisms of TNBC metastasis, and represent a potential treatment target for patients with TNBC.