MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway
Authors: Lianhong Li
Le Kang
Baoxue Yang
Jiazhi Li
Bo Song
Ying Lu
Jun Mao
Lijing Zhao
Yajun Tao
Wei Ma
Journal: Cancer science (2015)
Discipline: CLINICAL MEDICINE
Keywords: Breast cancer stem cell; Notch1; drug resistance; miR-34a; paclitaxel.
Affiliations: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, China., Department of Pathophysiology, Medical College of Dalian University, Dalian, China., Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, China., Department of Pharmacology, School of Basic Medical Sciences, Peking University and State Key Laboratory of Natural and Biomimetic Drugs, Beijing, China.

Abstract:  MicroRNAs play pivotal roles in cancer stem cell regulation. Previous studies have shown that microRNA-34a (miR-34a) is downregulated in human breast cancer. However, it is unknown whether and how miR-34a regulates breast cancer stem cells. 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. We reported that miR-34a negatively regulated cell proliferation, migration, and invasion and breast cancer stem cell propagation by downregulating Notch1. The expression of miR-34a was negatively correlated with tumor stages, metastasis, and Notch1 expression in breast cancer tissues. Furthermore, overexpression of miR-34a increased chemosensitivity of breast cancer cells to paclitaxel (PTX) by downregulating the Notch1 pathway. 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. Taken together, our results indicate that miR-34a inhibited breast cancer stemness and increased the chemosensitivity to PTX partially by downregulating the Notch1 pathway, suggesting that miR-34a/Notch1 play an important role in regulating breast cancer stem cells. Thus miR-34a is a potential target for prevention and therapy of breast cancer. 

Retracted: No

PubPeer comments:
 The proportion of renal abnormality in Enterococcal UTI should be 14 22 rather than the stated 14 20. Thus comparing to Gram-negative UTI, the proportion of renal abnormality is not significant (p=0.06), instead of the conclusion in this paper claiming p=0.03. , 
 The authors had the conclusion of  ...compared with Gram-negative UTI, enterococcal UTI was associated with male predominance, higher rates of underlying urinary abnormalities (70 vs. 43.7%; p=0.03)... However, from Table 2, the first variable  underlying renal abnormality stated 14 20 (70.0%) in Enterococcal UTI was wrong, as it should include individuals who received voiding cystourethrography and or ultrasonography (2nd and 3rd variable), which should be 14 22 (63.6%). When comparing to gram-negative UTI, Enterococcal UTI then did not have significant difference in proportion of underlying renal abnormality (14 22 vs 141 323, by chi-square test the p value is 0.06 instead of the 0.03 that authors stated). Willing to hear explanations from the authors. ,