Abstract | BACKGROUND: OBJECTIVE: To investigate whether the activation of NF-κB signaling could inhibit the expression of miR-124, possibly contributing to the pathogenesis of DLBCL. METHODS: Potential transcription factors regulating miR-124 transcription were predicted using the Transfac software. The cellular effects of NF-κB p65 on miR-124 were examined by MTS assay, Western blot assay, qPCR, and chromatin immunoprecipitation (ChIP) assays using DLBCL cell lines. RESULTS: Inhibition of NF-κB signals using Bay11-7085 increased miR-124 expression whereas exposure to TNF-α decreased it. Ectopic expression of p65 suppressed miR-124 expression, suggesting that p65 may be a transcriptional repressor of miRNA-124. Pharmacological analyses showed that phosphorylated/activated p65 downregulates miR-124 via two signaling pathways: (1) TAK1/IKKα-IKKβ/IκBα and (2) MAPK/p65. Moreover, ChIP assay demonstrated that p65 directly regulates miR-124 by binding to the NF-κB consensus sequence in its promoter region. Finally, we also confirmed that stable ectopic expression of miR-124 suppresses cell proliferation and survival. CONCLUSION: Taken together, our study uncovered a mechanism by which active NF-κB signaling disrupts the function of miR-124 as a tumor suppressor in DLBCL.
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Authors | Hyein Shim, Jehyun Nam, Sang-Woo Kim |
Journal | Genes & genomics
(Genes Genomics)
Vol. 42
Issue 5
Pg. 543-551
(05 2020)
ISSN: 2092-9293 [Electronic] Korea (South) |
PMID | 32207045
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MIRN124 microRNA, human
- MicroRNAs
- Transcription Factor RelA
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Topics |
- Animals
- Cell Line, Tumor
- Gene Expression Regulation, Neoplastic
- Humans
- Lymphoma, Large B-Cell, Diffuse
(genetics, metabolism)
- Mice
- MicroRNAs
(genetics, metabolism)
- Transcription Factor RelA
(genetics, metabolism)
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