Published online Apr 26, 2018. doi: 10.4252/wjsc.v10.i4.34
Peer-review started: March 6, 2018
First decision: March 13, 2018
Revised: March 21, 2018
Accepted: April 10, 2018
Article in press: April 10, 2018
Published online: April 26, 2018
To examine whether nuclear factor kappa B (NF-κB) activity regulates LIN28B expression and their roles in leukemia stem cell (LSC)-like properties.
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.
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.
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.
Core tip: In this study, we uncovered that LIN28B is regulated by nuclear factor kappa B (NF-κB) activity on transcriptional level and important for NF-κB-mediated leukemia-stem cell like properties of acute myeloid leukemia cells. NF-κB/LIN28B represents an attractive therapeutic target.