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Abstract
Competitive endogenous RNA (ceRNA) plays a vital role in cancer stem cells. In the present study, we aimed to investigate the role of the circular RNA (circRNA) antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as) during competitive inhibition of microRNA-7 (miR-7) in the regulation of autophagy to modulate the proliferation and migration of breast cancer stem cells. The CD44+/CD24- phenotype breast cancer stem cells were sorted from the original MCF7 cell by flow cytometry. RT-qPCR was applied to assess the expression of CDR1as and miR-7 in MCF7-Parent and MCF7-Stem cells. The activity of autophagy was evaluated followed the knockdown and overexpression of CDR1as. The correlation between CDR1as and miR-7 and between CDR1as and miR-7-target mRNAs were evaluated. This study revealed that CDR1as overexpression was associated with up-regulation of autophagy and that CDR1as competitive inhibition of miR-7 enhanced the LKB1-AMPK-mTOR signaling and autophagy-associated genes in breast cancer stem cells. CDR1as promoted the cell growth and migration of breast CSCs via the CDR1as/miR-7 axis, and knockdown of CDR1as and miR-7 overexpression obviously impaired the ability of growth and migration. The present study added a new view of developing a new therapeutic strategy against breast cancer.
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Details
1 Department of General surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, People’s Republic of China; Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
2 Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
3 Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
4 Department of General surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, People’s Republic of China