Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.656628
Keywords
super enhancer; FOSL1; miR-21-5p; head and neck squamous cell carcinoma; metastasis
Categories
Funding
- National Natural Science Foundation of China [82073265, 81572661, 81772889]
- Guangdong Financial Fund for High-Caliber Hospital Construction [174-2018-XMZC-0001-03-0125/D-14]
- Natural Science Foundation of Guangdong Province [2017A030313515, 2017A030313558]
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MiR-21-5p, an oncogenic miRNA, is upregulated in many solid cancers through a super-enhancer associated with the MIR21 gene (MIR21-SE). The key transcription factor FOSL1 directly controls miR-21-5p expression by interacting with MIR21-SE in head and neck squamous cell carcinoma (HNSCC). Clinical studies confirmed a positive correlation between miR-21-5p expression and FOSL1 expression, suggesting a potential role of FOSL1-SE in driving miR-21-5p expression to promote malignant progression of HNSCC.
MiR-21-5p is one of the most common oncogenic miRNAs that is upregulated in many solid cancers by inhibiting its target genes at the posttranscriptional level. However, the upstream regulatory mechanisms of miR-21-5p are still not well documented in cancers. Here, we identify a super-enhancer associated with the MIR21 gene (MIR21-SE) by analyzing the MIR21 genomic regulatory landscape in head and neck squamous cell carcinoma (HNSCC). We show that the MIR21-SE regulates miR-21-5p expression in different HNSCC cell lines and disruption of MIR21-SE inhibits miR-21-5p expression. We also identified that a key transcription factor, FOSL1 directly controls miR-21-5p expression by interacting with the MIR21-SE in HNSCC. Moreover, functional studies indicate that restoration of miR-21-5p partially abrogates FOSL1 depletion-mediated inhibition of cell proliferation and invasion. Clinical studies confirmed that miR-21-5p expression is positively correlated with FOSL1 expression. These findings suggest that FOSL1-SE drives miR-21-5p expression to promote malignant progression of HNSCC
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