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

Autor:	Zhou J; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Chooi JY; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore., Ching YQ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Quah JY; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Toh SH; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Ng Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Tan TZ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore., Chng WJ; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Jazyk:	angličtina
Zdroj:	World journal of stem cells [World J Stem Cells] 2018 Apr 26; Vol. 10 (4), pp. 34-42.
DOI:	10.4252/wjsc.v10.i4.34
Abstrakt:	Aim: To examine whether nuclear factor kappa B (NF-κB) activity regulates LIN28B 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 LIN28B. Western blot and qRT-PCR was employed to determine their protein and mRNA levels. Luciferase reporter was constructed and applied to explore the transcriptional regulation of LIN28B. We manipulated LIN28B 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 LIN28B in AML cells through drug inhibition and overexpression experiments. Notably, inhibition of NF-κB by pharmacological inhibitors reduced LIN28B expression and decreased cell proliferation. We demonstrated that NF-κB binds to the -819 to -811 region of LIN28B promoter, and transcriptionally regulates LIN28B expression. LIN28B protein was significantly elevated in NFκB1 transfected cells compared to vector control. Importantly, ectopic expression of LIN28B partially rescued the self-renewal capacity impaired by pharmacological inhibition of NF-κB activity. Conclusion: These results uncover a regulatory signaling, NF-κB/LIN28B, 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. Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Databáze:	MEDLINE
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