MiR-454-3p promotes apoptosis and autophagy of AML cells by targeting ZEB2 and regulating AKT/mTOR pathway
Xiao Wang,
Liang Zhong,
Wenran Dan,
Xuan Chu,
Xu Luo,
Chen Liu,
Peng Wan,
Yang Lu,
Zhenyan Liu,
Zhonghui Zhang,
Beizhong Liu
Affiliations
Xiao Wang
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Liang Zhong
Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
Wenran Dan
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Xuan Chu
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Xu Luo
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Chen Liu
Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
Peng Wan
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Yang Lu
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Zhenyan Liu
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Zhonghui Zhang
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
Beizhong Liu
Central Laboratory of Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
ABSTRACTBackground miR-454-3p is considered to have a crucial role in cancer progression, but the potential involvement in acute myeloid leukemia (AML) remains unclear.Methods Expression of miR-454-3p and ZEB2 mRNA and protein were quantified in AML cell lines. Cells were transfected with miR-454-3p inhibitor or mimic and cell growth was assessed by colony formation and CCK-8 assays and the cell cycle, apoptosis and autophagy were investigated by Western blotting, flow cytometry, immunofluorescence and 3-methyladenine (3-MA) treatment.Results miR-454-3p expression was attenuated in AML cells. miR-454-3p overexpression attenuated cell growth and stimulated cell cycle arrest, apoptosis and autophagy. Dual-luciferase reporter assays and bioinformatics analysis showed that AML progression was inhibited when miR-454-3p regulated ZEB2, an effect confirmed by rescue assays. 3-MA reduced the autophagy-inducing effect of ZEB2 knockdown and indicated that autophagy induced apoptosis. miR-454-3p downregulated p-mTOR/p-AKT levels in AML cells.Conclusion The novel role of miR-454-3p as a tumor inhibitor in AML via regulation of the ZEB2/AKT/mTOR axis was demonstrated, indicating miR-454-3p as a potential new molecular target for AML.
