| First Author | Liu B | Year | 2018 |
| Journal | Theranostics | Volume | 8 |
| Issue | 21 | Pages | 5801-5813 |
| PubMed ID | 30613263 | Mgi Jnum | J:295163 |
| Mgi Id | MGI:6459705 | Doi | 10.7150/thno.29380 |
| Citation | Liu B, et al. (2018) miR-200c/141 Regulates Breast Cancer Stem Cell Heterogeneity via Targeting HIPK1/beta-Catenin Axis. Theranostics 8(21):5801-5813 |
| abstractText | Increasing evidence demonstrates the existence of two inter-convertible states of breast cancer stem cells (BCSCs) with distinct behaviors in proliferation and mobility, and the BCSC heterogeneity is accurately regulated by sophisticated mechanisms including microRNAs. The microRNA-200 family including miR-200c/141 cluster was reported to affect cancer cell invasion and metastasis by regulating epithelial to mesenchymal transition (EMT). However, the effect of miR-200 family on BCSC heterogeneity is uncertain. Thus, we investigated whether the miR-200c/141 cluster had different effects on breast tumor growth and metastasis by switching the two states of BCSC. Methods: The spontaneous mammary tumor mouse model with miR-200c/141 conditional knockout was utilized for analyzing the role of miR-200c/141 cluster in vivo. The effect of miR-200c/141 cluster on BCSCs was performed by CD24/CD29 staining and ALDEFLUOR assay. miR-200c/141 target expression and EMT-related marker expression were verified in tumor sections, primary cells and breast cancer cell lines by qRT-PCR or western blotting. Statistical analysis was determined using two-way ANOVA and Student's t-test. All values were presented as the mean +/- s.e.m. Results: The deletion of miR-200c/141 cluster regulated BCSC heterogeneity and promoted the EMT-like BCSC generation, which resulted in increased tumor metastasis and inhibited tumor growth by directly upregulating the target gene homeodomain-interacting protein kinase 1 (HIPK1) and sequential beta-catenin activation. Conclusions: Our results indicated that miR-200c/141 played biphasic roles in breast tumor progression via affecting the BCSC heterogeneity, suggesting targeting BCSC heterogeneity to simultaneously restrict breast cancer initiation and metastasis could be a promising therapeutic strategy for breast cancer. |
