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FLI1 regulates inflammation-associated genes to accelerate leukemogenesis
Beiling Chen1, Danmei Sheng1, Chunlin Wang1
1State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, Guizhou Province, People's Republic of China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, Guizhou Province, People's Republic of China.
Cellular Signalling
|February 1, 2022
Summary
The ETS transcription factor FLI1 drives inflammation in leukemia by regulating key inflammatory genes like TNF and IL1B. Targeting these FLI1-induced inflammatory pathways offers a new strategy for treating leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Inflammation is crucial in cancer development and progression.
- The ETS transcription factor FLI1 is implicated in various cancers, but its role in inflammation is unclear.
Purpose of the Study:
- To investigate the role of FLI1 in inducing the inflammatory pathway in erythroleukemia cells.
- To identify specific inflammatory genes regulated by FLI1.
Main Methods:
- RNA sequencing (RNAseq) analysis to identify FLI1 transcriptional targets.
- Promoter binding assays to confirm direct regulation.
- Network analysis to identify interacting genes.
- Pharmacological inhibition of key inflammatory mediators.
Main Results:
- FLI1 induces the inflammatory pathway in erythroleukemia cells.
- FLI1 regulates TNF (indirectly via SPI1/PU.1) and IL1B (directly).
- Inhibition of TNF reduced leukemia cell proliferation.
- FLI1 negatively regulates IL1B-interacting proteins FOS, JUN, JUNB, and CASP1.
- Inhibitors of AP1 and CASP1 accelerated FLI1-dependent leukemia progression.
Conclusions:
- FLI1 plays a significant role in regulating the inflammatory pathway in leukemia.
- Targeting inflammatory genes downstream of FLI1 presents a novel therapeutic strategy for leukemia associated with FLI1 overexpression.
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