Zhou J, Chooi JY, Ching YQ, Quah JY, Toh SHM, Ng Y, Tan TZ, Chng WJ. NF-κB promotes the stem-like properties of leukemia cells by activation of LIN28B. World J Stem Cells 2018; 10(4): 34-42 [PMID: 29707103 DOI: 10.4252/wjsc.v10.i4.34]
Corresponding Author of This Article
Jianbiao Zhou, MD, PhD, Senior Scientist, Cancer Science Institute of Singapore, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. csizjb@nus.edu.sg
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jianbiao Zhou, 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, Singapore 117599, Singapore
Jianbiao Zhou, Jing-Yuan Chooi, Wee-Joo Chng, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
Wee-Joo Chng, Department of Hematology-Oncology, National University Cancer Institute, Singapore 119228, Singapore
Author contributions: Zhou J and Chng WJ conceptualized the original idea, designed the experiments and analyzed the data; Zhou J performed the experiments, wrote the paper; Chooi JY, Ching YQ, Quah JY, Toh SHM and Ng Y performed the experiments; Tan TZ conducted the bioinformatics analysis; all authors read and approved the final manuscript.
Supported by the Singapore National Research Foundation and the Ministry of Education under the Research Center of Excellence Program to WJ Chng and NMRC Clinician-Scientist IRG Grant CNIG11nov38 (Zhou J); Chng WJ is also supported by NMRC Clinician Scientist Investigator award; This study is also partially supported by the RNA Biology Center at CSI Singapore, NUS, from funding by the Singapore Ministry of Education’s Tier 3 Grants, No. MOE2014-T3-1-006.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: The datasets supporting the conclusions of this article are included within the article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jianbiao Zhou, MD, PhD, Senior Scientist, Cancer Science Institute of Singapore, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. csizjb@nus.edu.sg
Telephone: +65-6-5161118
Received: March 6, 2018 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 Processing time: 51 Days and 17.6 Hours
Abstract
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.
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.
