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53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.

Kong X, Ding X, Li X, Gao S, Yang Q - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.

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Related in: MedlinePlus

53BP1 inhibited ZEB1 expression by targeting miR-200b and miR-429 in breast cancer cell lines. (a) Changes in miRNA expression levels as measured by quantitative RT-PCR. (b) MDA-MB-231-53BP1 overexpressed cell lysates transfected with miR-control (Con) and miR-200b/429 inhibitors (Inh) were subjected to Western blot analysis. (c) MCF-7-sh53BP1 cell lysates transfected with miR-Control (Con) and miR-200b/429 mimics were subjected to Western blot analysis. (d) Regulation of miR-200b and -429 after transfecting siRNAs of ZEB1 in MCF-7-sh53BP1 cells. All experiments were carried out in triplicate, at minimum. Error bars, ±SEM. *P < 0.05, **P < 0.01 versus control (Student’s t-test).
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fig03: 53BP1 inhibited ZEB1 expression by targeting miR-200b and miR-429 in breast cancer cell lines. (a) Changes in miRNA expression levels as measured by quantitative RT-PCR. (b) MDA-MB-231-53BP1 overexpressed cell lysates transfected with miR-control (Con) and miR-200b/429 inhibitors (Inh) were subjected to Western blot analysis. (c) MCF-7-sh53BP1 cell lysates transfected with miR-Control (Con) and miR-200b/429 mimics were subjected to Western blot analysis. (d) Regulation of miR-200b and -429 after transfecting siRNAs of ZEB1 in MCF-7-sh53BP1 cells. All experiments were carried out in triplicate, at minimum. Error bars, ±SEM. *P < 0.05, **P < 0.01 versus control (Student’s t-test).

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.


53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.

Kong X, Ding X, Li X, Gao S, Yang Q - Cancer Sci. (2015)

53BP1 inhibited ZEB1 expression by targeting miR-200b and miR-429 in breast cancer cell lines. (a) Changes in miRNA expression levels as measured by quantitative RT-PCR. (b) MDA-MB-231-53BP1 overexpressed cell lysates transfected with miR-control (Con) and miR-200b/429 inhibitors (Inh) were subjected to Western blot analysis. (c) MCF-7-sh53BP1 cell lysates transfected with miR-Control (Con) and miR-200b/429 mimics were subjected to Western blot analysis. (d) Regulation of miR-200b and -429 after transfecting siRNAs of ZEB1 in MCF-7-sh53BP1 cells. All experiments were carried out in triplicate, at minimum. Error bars, ±SEM. *P < 0.05, **P < 0.01 versus control (Student’s t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4556386&req=5

fig03: 53BP1 inhibited ZEB1 expression by targeting miR-200b and miR-429 in breast cancer cell lines. (a) Changes in miRNA expression levels as measured by quantitative RT-PCR. (b) MDA-MB-231-53BP1 overexpressed cell lysates transfected with miR-control (Con) and miR-200b/429 inhibitors (Inh) were subjected to Western blot analysis. (c) MCF-7-sh53BP1 cell lysates transfected with miR-Control (Con) and miR-200b/429 mimics were subjected to Western blot analysis. (d) Regulation of miR-200b and -429 after transfecting siRNAs of ZEB1 in MCF-7-sh53BP1 cells. All experiments were carried out in triplicate, at minimum. Error bars, ±SEM. *P < 0.05, **P < 0.01 versus control (Student’s t-test).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.

Show MeSH
Related in: MedlinePlus