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Mol Cancer Ther. 2019 Sep 12. pii: molcanther.0051.2019. doi: 10.1158/1535-7163.MCT-19-0051. [Epub ahead of print]

Morin inhibits proliferation and induces apoptosis by modulating miR-188-5p/PTEN/AKT regulatory pathway in CML cells.

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Department of Hematology, Second Hospital of Hebei Medical University.
Department of Urology, Second Hospital of Hebei Medical University.
The Key Laboratory of Neural and Vascular Biology,Ministry of Education of China, Hebei Medical University.
Department of Hematology, Second Hospital of Hebei Medical University


Increased activity of PI3K/AKT/mTOR pathway has been observed in chronic myeloid leukemia (CML). Morin, a kind of flavonoid, exhibits a significant anticancer activity by suppressing the PI3K/AKT signaling pathway. However, the effect of morin on CML and its underlying mechanisms are poorly understood. Here, we found that morin dose-dependently inhibited the proliferation of CML cell lines K562 and KCL22 and induced their apoptosis, with a significant increase in cell apoptosis upon exposure of cells to 50 μM morin. Moreover, morin significantly reduced CML xenograft growth in nude mice. Mechanically, morin attenuated phosphorylated AKT level by upregulating PTEN expression, thus leading to the inhibition of AKT signaling. Knockdown of PTEN by its si-RNA completely abrogated morin-induced cell apoptosis, indicating that PTEN mediates the inductive effect of morin on CML cell apoptosis. More importantly, we found that miR-188-5p was significantly upregulated in CML patients and CML cell lines. Treating CML cells with morin markedly downregulated miR-188-5p expression level. Further, we demonstrated that miR-188-5p repressed PTEN expression by directly targeting its 3'-UTR. miR-188-5p downregulation induced by morin enhanced CML cell apoptosis by relieving miR-188-5p repression of PTEN expression. In summary, morin exerts significant anticancer efficacy in CML by regulating miR-188-5p/PTEN axis and thus repressing the PI3K/AKT signaling.

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