Limits...
MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.

Kang L, Mao J, Tao Y, Song B, Ma W, Lu Y, Zhao L, Li J, Yang B, Li L - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.

Show MeSH

Related in: MedlinePlus

MicroRNA-34a (MiR-34a) expression is downregulated in breast cancer tissues and negatively correlated with tumor stage, metastasis, and expression of Notch1. (a) MiR-34a expression (exp) in 45 cases of human breast cancer and 16 normal adjacent tissues (NATs) (P < 0.05). (b) MiR-34a expression is associated with lymph node metastasis of breast cancer (P < 0.05). (c) MiR-34a expression in different clinical stages of breast cancer patients. Statistical analyses were carried out using Student's t-test (a–c). (d) Inverse correlation between miR-34a and Notch1 mRNA expression in breast cancer tissues (n = 45) by Spearman's correlation analysis. (e) Representative immunohistochemical analyses of Notch1 in normal breast tissue and breast cancer tissue with different Notch1 scores (×100). (f) Immunohistochemistry scores of Notch1 in NATs and breast cancer tissues. (g) MiR-34a expression negatively correlated with Notch1 scores in breast cancer tissues. (Spearman's correlation analysis, r = −0.692; P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4471794&req=5

fig02: MicroRNA-34a (MiR-34a) expression is downregulated in breast cancer tissues and negatively correlated with tumor stage, metastasis, and expression of Notch1. (a) MiR-34a expression (exp) in 45 cases of human breast cancer and 16 normal adjacent tissues (NATs) (P < 0.05). (b) MiR-34a expression is associated with lymph node metastasis of breast cancer (P < 0.05). (c) MiR-34a expression in different clinical stages of breast cancer patients. Statistical analyses were carried out using Student's t-test (a–c). (d) Inverse correlation between miR-34a and Notch1 mRNA expression in breast cancer tissues (n = 45) by Spearman's correlation analysis. (e) Representative immunohistochemical analyses of Notch1 in normal breast tissue and breast cancer tissue with different Notch1 scores (×100). (f) Immunohistochemistry scores of Notch1 in NATs and breast cancer tissues. (g) MiR-34a expression negatively correlated with Notch1 scores in breast cancer tissues. (Spearman's correlation analysis, r = −0.692; P < 0.05).

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.


MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.

Kang L, Mao J, Tao Y, Song B, Ma W, Lu Y, Zhao L, Li J, Yang B, Li L - Cancer Sci. (2015)

MicroRNA-34a (MiR-34a) expression is downregulated in breast cancer tissues and negatively correlated with tumor stage, metastasis, and expression of Notch1. (a) MiR-34a expression (exp) in 45 cases of human breast cancer and 16 normal adjacent tissues (NATs) (P < 0.05). (b) MiR-34a expression is associated with lymph node metastasis of breast cancer (P < 0.05). (c) MiR-34a expression in different clinical stages of breast cancer patients. Statistical analyses were carried out using Student's t-test (a–c). (d) Inverse correlation between miR-34a and Notch1 mRNA expression in breast cancer tissues (n = 45) by Spearman's correlation analysis. (e) Representative immunohistochemical analyses of Notch1 in normal breast tissue and breast cancer tissue with different Notch1 scores (×100). (f) Immunohistochemistry scores of Notch1 in NATs and breast cancer tissues. (g) MiR-34a expression negatively correlated with Notch1 scores in breast cancer tissues. (Spearman's correlation analysis, r = −0.692; P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4471794&req=5

fig02: MicroRNA-34a (MiR-34a) expression is downregulated in breast cancer tissues and negatively correlated with tumor stage, metastasis, and expression of Notch1. (a) MiR-34a expression (exp) in 45 cases of human breast cancer and 16 normal adjacent tissues (NATs) (P < 0.05). (b) MiR-34a expression is associated with lymph node metastasis of breast cancer (P < 0.05). (c) MiR-34a expression in different clinical stages of breast cancer patients. Statistical analyses were carried out using Student's t-test (a–c). (d) Inverse correlation between miR-34a and Notch1 mRNA expression in breast cancer tissues (n = 45) by Spearman's correlation analysis. (e) Representative immunohistochemical analyses of Notch1 in normal breast tissue and breast cancer tissue with different Notch1 scores (×100). (f) Immunohistochemistry scores of Notch1 in NATs and breast cancer tissues. (g) MiR-34a expression negatively correlated with Notch1 scores in breast cancer tissues. (Spearman's correlation analysis, r = −0.692; P < 0.05).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China.

Show MeSH
Related in: MedlinePlus