scholarly journals Genome-Wide Enhancer Analysis Reveals the Role of AP-1 Transcription Factor in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Chen-Yu Wang ◽  
Guang-Tao Yu ◽  
Chuan Gao ◽  
Ji Chen ◽  
Qing-Lan Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Conditional Knockout ◽  
Neck Squamous Cell Carcinoma ◽  
Motif Analysis ◽  
Super Enhancer ◽  
Genome Wide

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but its epigenomic features have not been determined. Here, we studied the chromatin landscape of active enhancers of HNSCC head tumor tissues by performing H3K27ac and H3K4me1 ChIP-Seq with a Tgfbr1/Pten double conditional knockout HNSCC mouse model. We identified 1,248 gain variant enhancer loci (VELs) and 2,188 lost VELs, as well as 153 gain variant super enhancer loci (VSELs) and 234 lost VSELs. Potentially involved transcription factors were predicted with motif analysis, and we identified AP-1 as one of the critical oncogenic transcription factors in HNSCC and many other types of cancer. Combining transcriptomic and epigenomic data, our analysis also showed that AP-1 and histone modifications coordinately regulate target gene expression in HNSCC. In conclusion, our study provides important epigenomic information for enhancer studies in HNSCC and reveals new mechanism for AP-1 regulating HNSCC.

scholarly journals A panel of Transcription factors identified by data mining can predict the prognosis of head and neck squamous cell carcinoma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Boxin Zhang ◽  
Haihui Wang ◽  
Ziyan Guo ◽  
Xinhai Zhang
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Clinicopathological Parameters

Abstract Background Transcription factors (TFs) are responsible for the regulation of various activities related to cancer like cell proliferation, invasion, and migration. It is thought that, the measurement of TFs levels could assist in developing strategies for diagnosis and prognosis of cancer detection. However, due to lack of effective genome-wide tests, this cannot be carried out in clinical settings. Methods A complete assessment of RNA-seq data in samples of a head and neck squamous cell carcinoma (HNSCC) cohort in The Cancer Genome Atlas (TCGA) database was carried out. From the expression data of six TFs, a risk score model was developed and further validated in the GSE41613 and GSE65858 series. Potential functional roles were identified for the six TFs via gene set enrichment analysis. Results Based on our multi-TF signature, patients are stratified into high- and low-risk groups with significant variations in overall survival (OS) (median survival 2.416 vs. 5.934 years, log-rank test P < 0.001). The sensitivity and specificity evaluation of our multi-TF for 3-year OS in TCGA, GSE41613 and GSE65858 was 0.707, 0.679 and 0.605, respectively, demonstrating good reproducibility and robustness for predicting overall survival of HNSCC patients. Through multivariate Cox regression analyses (MCRA) and stratified analyses, we confirmed that the predictive capability of this risk score (RS) was not dependent on any of other factors like clinicopathological parameters. Conclusions With the help of a RS obtained from a panel of TFs expression signatures, effective OS prediction and stratification of HNSCC patients can be carried out.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuehan Wan ◽  
Rosalie G. Hoyle ◽  
Nan Xie ◽  
Wenjin Wang ◽  
Hongshi Cai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Target Genes ◽  
Neck Squamous Cell Carcinoma ◽  
Functional Studies ◽  
Super Enhancer ◽  
Posttranscriptional Level ◽  
Proliferation And Invasion

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

scholarly journals LIM Homeobox Transcription Factors as Novel Prognosis Biomarkers in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chen Lu ◽  
Cong-cong Duan ◽  
Han Bing
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Clinical Variables

Abstract Background: LIM class homeobox (LHX) genes, an important subfamily of the homeobox genes, encode transcription factors that have a fundamental role during embryonic development. However, knowledge regarding the function and mechanism of LHXs in head and neck squamous cell carcinoma (HNSCC) is still lacking. Methods: We conduct a bioinformatic analysis to systematically explore the mRNA expression, clinical correlation, prognostic values, and underlying mechanisms of distinct LHXs in HNSCC. The differentially expressed mRNAs in the LIM homeobox gene family and their correlation with clinical variables were determined and verified with packages in software R. The prognosis values of LHXs expression levels were evaluated by Kaplan-Meier (KM) method and Cox proportional hazard model. Gene set enrichment analysis (GSEA) was conducted to understand the potential biological function of LHXs. The immune cell infiltration patterns were estimated through CIBERSORT and TIMER, and the methylation levels of LHXs in HNSCC were explored in UALCAN and MEXPRESS.Results: We found that among 12 LHXs, 8 genes (ISL1, LHX1-3, 5, 9, LMX1A, and LMX1B) showed altered expression in HNSCC tissues and detected significant correlations between their expression and clinical variables. Survival analysis revealed that LHX1, LHX5, LMX1A, LMX1B can serve as unfavorable prognosis predictors, and ISL1, LHX2, LHX9 can serve as favorable predictors in all HNSCC patients. Gene sets enrichment analysis and immune infiltration analyses showed that the aberrant expression of LHXs was closely related to cancer-associated processes and immune cell infiltration patterns. Finally, we observed hyper-methylation in the promoters of ISL1, LHX2, 5, 9, LMX1A, LMX1B and hypo-methylation in LHX3 promoter, suggesting the regulatory mechanism of LHXs abnormal expression may be related to aberrant DNA methylation. Conclusions: Our study found the oncogenic roles of LHX1,5 and LMX1B and the tumor-suppressor roles of ISL1 and LHX2 in patients with HNSCC, suggesting these LHXs as novel diagnostic and prognostic biomarkers for HNSCC.

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