Journal article
Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia
- Abstract:
- Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 5.3MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41375-022-01801-z
Authors
- Publisher:
- Springer Nature
- Journal:
- Leukemia More from this journal
- Volume:
- 37
- Issue:
- 2
- Pages:
- 276-287
- Place of publication:
- England
- Publication date:
- 2022-12-26
- Acceptance date:
- 2022-12-15
- DOI:
- EISSN:
-
1476-5551
- ISSN:
-
0887-6924
- Pmid:
-
36572750
- Language:
-
English
- Keywords:
- Pubs id:
-
1318179
- Local pid:
-
pubs:1318179
- Deposit date:
-
2024-01-10
Terms of use
- Copyright holder:
- Rastogi et al
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record