2. Academic Validation
  3. A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma

A Super-Enhancer Driven by FOSL1 Controls miR-21-5p Expression in Head and Neck Squamous Cell Carcinoma

  • Front Oncol. 2021 Apr 16;11:656628. doi: 10.3389/fonc.2021.656628.
Yuehan Wan 1 2,  Rosalie G Hoyle 3,  Nan Xie 2 4,  Wenjin Wang 1 2,  Hongshi Cai 1 2,  Ming Zhang 1 2,  Zhikun Ma 3,  Gan Xiong 1 2,  Xiuyun Xu 1 2,  Zhengxian Huang 1 2,  Xiqiang Liu 5,  Jiong Li 3 6,  Cheng Wang 1 2
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
  • 2 Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, China.
  • 3 Department of Medicinal Chemistry, Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
  • 4 Department of Oral Pathology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China.
  • 5 Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 6 Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, United States.
PMID: 33937067 DOI: 10.3389/fonc.2021.656628
Abstract

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.

Keywords

FOSL1; head and neck squamous cell carcinoma; metastasis; miR-21-5p; super enhancer.

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