Abstract
Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44+/CD24- breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo, at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.
Highlights
Breast cancer is the most common cancer with high morbidity and mortality, and the leading cause of cancer death in females worldwide [1]
Levels of the endogenous expression of the miR-34a and the SIRT1 in CD44+/CD24− Breast cancer stem cells (BCSCs) was estimated by using relative quantitative real time RT-PCR (qRT-PCR)
The SIRT1 protein expression level further confirmed by western blot in CD44+/CD24− BCSCs (Figure 1C), which was verified by immunofluorescence analysis (Figure 1D)
Summary
Breast cancer is the most common cancer with high morbidity and mortality, and the leading cause of cancer death in females worldwide [1]. Prognosis of breast cancer has been significantly improved last decades by many effective adjuvant therapies, recurrence and relapse remain still major challenge in the treatment of this disease. Growing evidence suggests that its recurrence and/or relapse may be initiated and maintained by remaining cancer stem cells (CSCs) from either residual tumors or those with intrinsic resistance to adjuvant therapy [2,3,4]. Breast cancer stem cells (BCSCs) with cell surface phenotype of CD44+/CD24−/low/Lineage−low were first identified and isolated by Al-Hajjet al. BCSCs used as therapeutic targets are getting more attention to the community of breast cancer treatment [7,8,9,10]
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