53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.
Bottom Line: Consistently, in MCF-7 breast cancer cells, low 53BP1 expression reduced E-cadherin expression, resulting in increased migration and invasion.These effects were reversed by miR-200b and miR-429 inhibition or overexpression.It was also found that 53BP1 was associated with lymph node metastasis.
Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.Show MeSH
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Mentions: We found that ZEB1 was regulated most significantly in the expression of EMT TFs that suppressed E-cadherin (Fig.1b). Thus, we speculated that 53BP1 mainly regulated EMT through targeting ZEB1. A review of published works revealed that the miR-200 family, including miR-200a/b/c, miR-141, and miR-429, were reported to directly target the E-cadherin transcriptional repressors ZEB1. Therefore, we detected the expression of the miR-200 family in MDA-MB-231-53BP1 cells and MCF-7-sh53BP1 cells compared with control cells. Using qRT-PCR, we confirmed that miR-200b and miR-429 were obviously upregulated in MDA-MB-231-53BP1 cells and decreased in MCF-7-sh53BP1 cells (Fig.3a). We also validated the expressions of other miRNAs that have potential binding sites for ZEB1 predicted by TargetScan, PicTar, Miranda, and miRDB, including miR-23b, miR-199a, miR-96, and miR-150. Results showed that some of these miRNAs were downregulated by 53BP1 knockdown and upregulated by 53BP1 overexpression. However, their expression changes by 53BP1 were not as significant as miR-200b and miR-429.
Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.