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NF-κB promotes the stem-like properties of leukemia cells by activation of LIN28B

World Journal of Stem Cells 2018年第4期10卷 34-42页

作者： Jianbiao Zhou Jing-Yuan Chooi Ying Qing Ching Jessie Yiying Quah sabrina hui-min toh Yvonne Ng Tuan Zea Tan Wee-Joo Chng Cancer Science Institute of Singapore National University of Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of Singapore Department of Hematology-Oncology National University Cancer Institute

AIM To examine whether nuclear factor kappa B(NF-κB) activity regulates LIN28 B expression and their roles in leukemia stem cell(LSC)-like properties. METHODS We used pharmacological inhibitor and cell viability assays to examine the relation between NF-κB and LIN28 B. Western blot and q RT-PCR was employed to determine their protein and m RNA levels. Luciferase reporter was constructed and applied to explore the transcriptional regulation of LIN28 B. We manipulated LIN28 B level in acute myeloid leukemia(AML) cells and investigated LSC-like properties with colony forming and serial replating assays. RESULTS This study revealed the relationship between NF-κB and LIN28 B in AML cells through drug inhibition and overexpression experiments. Notably,inhibition of NF-κB by pharmacological inhibitors reduced LIN28 B expression and decreased cell proliferation. We demonstrated that NF-κB binds to the-819 to-811 region of LIN28 B promoter,and transcriptionally regulates LIN28 B expression. LIN28 B protein was significantly elevated in NFκB1 transfected cells compared to vector control. Importantly,ectopic expression of LIN28 B partially rescued the self-renewal capacity impaired by pharmacological inhibition of NF-κB activity. CONCLUSION These results uncover a regulatory signaling,NF-κB/LIN28 B,which plays a pivotal role in leukemia stem cell-like properties and it could serve as a promising intervening target for effective treatment of AML disease.

关键词： Nuclear factor kappa B LIN28B Leukemia stem cell Acute myeloid leukemia

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