1. Berberine promotes XIAP-mediated cells apoptosis by upregulation of miR-24-3p in acute lymphoblastic leukemia.
- Author
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Liu J, Chen Z, Cui Y, Wei H, Zhu Z, Mao F, Wang Y, and Liu Y
- Subjects
- Animals, Bone Marrow drug effects, Bone Marrow metabolism, Cell Line, Tumor, Cell Survival drug effects, Humans, Mice, Up-Regulation drug effects, Apoptosis drug effects, Berberine pharmacology, MicroRNAs metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, X-Linked Inhibitor of Apoptosis Protein metabolism
- Abstract
Background: Berberine (BBR) has gained considerable attention because of its anti-tumor activity. BBR can induce apoptosis of acute lymphoblastic leukemia (ALL) cells through the MDM2/p53 pathway. However, the effects of BBR on those ALL patients with p53 deficiency remain unclear., Results: We found that BBR reduced ALL cell viability and induced apoptosis in p53-null EU-4 and p53-mutant EU-6 cells by downregulating X-linked inhibitor of apoptosis protein (XIAP), which is increased in ALL tissues and cells. BBR-induced cell apoptosis was attenuated by inhibition of XIAP that was controlled by PIM-2. Mechanistic studies showed that BBR treatment induced an enhancement of miR-24-3p. PIM-2 is a direct target of miR-24-3p. Blockade of PIM-2 or miR-24-3p reversed BBR-induced cell apoptosis. In vivo studies, BBR remarkably alleviated leukemia conditions in a EU4 xenograft mouse model, whereas inhibition of miR-24-3p significantly reversed the effects of BBR in the leukemia condition., Conclusions: miR-24-3p/PIM-2/XIAP signaling contributes to BBR-mediated leukemia mitigation in p53-defect ALL, which should be further developed as a treatment strategy in ALL patients with p53 deficiency., Methods: Cell viability and apoptosis were determined using CCK-8 and TUNEL assays, respectively. The dual-luciferase reporter gene system was used to determine the interaction between miR-24-3p and 3'-untranslated regions (UTRs) of PIM-2.
- Published
- 2020
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