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| Honokiol-induced degradation of AML1-ETO oncoprotein through upregulation of UbcH8 in acute myeloid leukemia |
| LI Haiying1, ZHOU Bin1, WU Jianbo1, XING Chongyun2. |
| 1.Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China |
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| Cite this article: |
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LI Haiying1,ZHOU Bin,WU Jianbo, et al. Honokiol-induced degradation of AML1-ETO oncoprotein through upregulation of UbcH8 in acute myeloid leukemia[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(5): 327-332.
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Abstract Objective: To investigate the possible mechanism of the degradation of AML1-ETO protein induced by honokiol. Methods: Kasumi-1 cells were treated with 10, 20 and 40 μmol/L honokiol for 24 h and 48 h. The mRNA expression of AML1-ETO and UbcH8 and the protein expression were detected by qRT-PCR and Western blot respectively. Microarry analysis was used to select the target gene. To explore the role of UbcH8 in the degradation of AML1-ETO protein induced by honokiol, the expression of UbcH8 was knocked down by small hairpin RNAs (shRNAs) and overexpressed by MSCV-based vector to detect the related indicators. A xenograft mice model was treated by honokiol to detect tumorigenicity and related protein expression. Results: Honokiol decreased the protein expression of AML1-ETO in a time- and concentration- dependent manner, and reduced the stability of AML1-ETO protein, but did not affect the mRNA expression of AML1-ETO in kasumi-1 cell. We identified UbcH8 as the target gene by honokiol through microarray analysis. Honokiol obviously increased the expression of UbcH8 by 4-fold. Furthermore, overexpression of UbcH8 decreased the expression of AML1-ETO and knockdown of UbcH8 by shRNAs prevented honokiol-induced degradation of AML-ETO, suggesting that UbcH8 plays a critical role in the degradation of AML1-ETO by honokiol. Finally, honokiol decreased xenograft tumor size in a xenograft leukemia mouse model. Meanwhile, the protein of AML1-ETO was significantly reduced, while UBCH8 expression was elevated. Conclusion: Honokiol can degrade AML1-ETO oncoprotein through upregulation of UbcH8 in acute myeloid leukemia.
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Received: 30 January 2019
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