Integrative Analysis of miRNAs Identifies Clinically Relevant Epithelial and Stromal Subtypes of Head and Neck Squamous Cell Carcinoma

Holt, Jeremiah; Walter, Vonn; Yin, Xiaoying; Marron, David; Wilkerson, Matthew D.; Choi, Hyo Young; Zhao, Xiaobei; Jo, Heejoon; Hayes, D. Neil; Ko, Yoon Ho

doi:10.1158/1078-0432.ccr-20-0557

Cited by 8 publications

(16 citation statements)

References 56 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All miR-200 members have been shown to play an important part in repressing malignant cell transformation and in inhibiting tumor initiation, and have thus been characterized as tumor suppressors [ 127 , 128 ]. More specifically, the miR-200 family has been reported to negatively modulate the progress of EMT in various cancers, including HNSCC [ 129 ], by controlling the expression of transcriptional repressors ZEB1 and ZEB2, the so-called EMT master regulators [ 126 , 130 , 131 ].…”

Section: The Role Of the Most Common Mirnas In Hncmentioning

confidence: 99%

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

Thomaidou

Batsaki

Adamaki

et al. 2022

IJMS

View full text Add to dashboard Cite

Head and neck cancers (HNCs) comprise a heterogeneous group of tumors that extend from the oral cavity to the upper gastrointestinal tract. The principal etiologic factors for oral tumors include tobacco smoking and alcohol consumption, while human papillomavirus (HPV) infections have been accused of a high incidence of pharyngeal tumors. Accordingly, HPV detection has been extensively used to categorize carcinomas of the head and neck. The diverse nature of HNC highlights the necessity for novel, sensitive, and precise biomarkers for the prompt diagnosis of the disease, its successful monitoring, and the timely prognosis of patient clinical outcomes. In this context, the identification of certain microRNAs (miRNAs) and/or the detection of alterations in their expression patterns, in a variety of somatic fluids and tissues, could serve as valuable biomarkers for precision oncology. In the present review, we summarize some of the most frequently studied miRNAs (including miR-21, -375, -99, -34a, -200, -31, -125a/b, -196a/b, -9, -181a, -155, -146a, -23a, -16, -29, and let-7), their role as biomarkers, and their implication in HNC pathogenesis. Moreover, we designate the potential of given miRNAs and miRNA signatures as novel diagnostic and prognostic tools for successful patient stratification. Finally, we discuss the currently ongoing clinical trials that aim to identify the diagnostic, prognostic, or therapeutic utility of miRNAs in HNC.

show abstract

Section: The Role Of the Most Common Mirnas In Hncmentioning

confidence: 99%

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

Thomaidou

Batsaki

Adamaki

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Although a significant progress on the pathogenesis of HNSCC has been made in the past decades, the exact molecular mechanisms are still not well understood. Increasing evidences implicates that dysregulation of miRNAs has a critical role in the development and progression of HNSCC (4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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

show abstract

“…One of the predicted targets of miR-203a in our analysis was Semaphorin 5a that is associated with lymph node metastasis and adverse prognosis [ 58 ]. Integrative Analysis of miRNAs in HNSCC has previously identified miR-194 to be associated with the epithelial sub-type of HNSCC [ 59 ]. However, to the best of our knowledge no study has shown the role of miR-203, miR-194 and miR-10a as a prognostic indicator of LVI in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers

et al. 2021

View full text Add to dashboard Cite

Lymphovascular invasion (LVI) is an important prognostic indicator of lymph node metastasis and disease aggressiveness but clear molecular mechanisms mediating this in head and neck cancers (HNSC) remain undefined. To identify important microRNAs (miRNAs) in HNSC that associate with and are also predictive of increased risk of LVI, we used a combination of clustering algorithms, multiple regression analyses and machine learning approaches and analyzed miRNA expression profiles in the TCGA HNSC database. As the first step, we identified miRNAs with increased association with LVI as a binary variable. In order to determine whether the identified miRNAs would show functional clusters that are also indicative of increased risk for LVI, we carried out unsupervised as well as supervised clustering. Our results identified distinct clusters of miRNAs that are predictive of increased LVI. We further refined these findings using a Random forest approach, and miR-203a-3p, mir-10a-5p, and miR-194-5p to be most strongly associated with LVI. Pathway enrichment analysis showed these miRNAs targeted genes involved in Hippo signaling and fatty acid oxidation pathways that are mediators of lymph node metastasis. Specific association was also identified between the miRNAs associated with LVI and expression of several lymphangiogenic genes that could be critical for determination of therapeutic strategies.

show abstract

Integrative Analysis of miRNAs Identifies Clinically Relevant Epithelial and Stromal Subtypes of Head and Neck Squamous Cell Carcinoma

Cited by 8 publications

References 56 publications

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

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

Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers

Contact Info

Product

Resources

About