Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 2, Pages 1405-1416Publisher
WILEY
DOI: 10.1002/jcp.29059
Keywords
breast cancer; cancer stem cells; miR-7; subpopulation
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Funding
- National Natural Science Foundation of China [81572887]
- National key Research and development Program of China [2017YFA0205502]
- Foundation of Nanjing science and technology development plan [2016sc512020]
- Scientific Research Foundation of Graduate School of Southeast University [YBJJ1746]
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Breast cancer patients with high expression of aldehyde dehydrogenases (ALDHs) cell population have higher tolerability to chemotherapy since the cells posses a characteristic of breast cancer stem cells (BCSCs) that are resistant to conventional chemotherapy. In this study, we found that the ALDH-positive cells were higher in CD44(+)CD24(-) and CD44(+)CD24(-)ESA(+)BCSCs than that in both BT549 and MDA-MB-231 cell lines but microRNA-7 (miR-7) level was lower in CD44(+)CD24(-) and CD44(+)CD24(-)ESA(+)BCSCs than that in MDA-MB-231 cells. Moreover, miR-7 overexpression in MDA-MB-231 cells decreased ALDH1A3 activity by miR-7 directly binding to the 3 '-untranslated region of ALDH1A3; while the ALDH1A3 expression was downregulated in MDA-MB-231 cells, the expressions of CD44 and Epithelium Specific Antigen (ESA) were reduced along with decreasing the BCSC subpopulation. Significantly, enforced expression of miR-7 in CD44(+)CD24(-)ESA(+)BCSC markedly inhibited the BCSC-driven xenograft growth in mice by decreasing an expression of ALDH1A3. Collectively, the findings demonstrate the miR-7 inhibits breast cancer growth via suppressing ALDH1A3 activity concomitant with decreasing BCSC subpopulation. This approach may be considered for an investigation on clinical treatment of breast cancers.
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