MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.
Bottom Line: Notch signaling is one of the most important pathways in stem cell maintenance and function.In this study, we verified that miR-34a directly and functionally targeted Notch1 in MCF-7 cells.Mammosphere formation and expression of the stemness factor ALDH1 were also reduced in the cells treated with miR-34a and PTX compared to those treated with PTX alone.
Affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.Show MeSH
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Mentions: To further study the importance of Notch1 repression by miR-34a, expression of miR-34a and Notch1 was examined in 45 breast cancer specimens and 16 normal adjacent breast tissues (NATs). The association between miR-34a expression and the clinicopathological parameters of breast cancer tissues is shown in Table1. The average expression of miR-34a was significantly downregulated in breast cancer tissues compared to the NATs (Fig.2a). MicroRNA-34a expression levels in patients with lymph node metastases (n = 27) was also lower than that in patients without lymph node metastases (n = 18) (Fig.2b). Additionally, we examined miR-34a expression in patients with different TNM stages. The level of miR-34a was reduced with progression of clinical stage, but no significant difference was observed between stage III and stage IV (Fig.2c). All the results indicated that reduced expression of miR-34a may play an important role in the initiation, progression, and metastasis of breast cancer. Notch1 expression was detected using qRT-PCR and IHC in all clinical specimens. Consistent with a recent report,27 Notch1 was found to be overexpressed in breast cancer tissues compared to NATs (Fig.2f). Moreover, an inverse correlation between the expression of miR-34a and Notch1 was observed (Fig.2d). In addition, analysis of IHC scores showed that Notch1 was negatively associated with miR-34a expression (Fig.2g). These results confirmed that the miR-34a/Notch1 pathway was essential in regulating breast cancer initiation and progression.
Affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.