Dysregulated microRNA Expression Relevant to TERT Promoter Mutations in Tonsil Cancer-A Pilot Study

Area of Science:

• Oncology
• Molecular Biology
• Virology

Background:

• Tonsillar squamous cell carcinomas (TSCCs) frequently test positive for human papillomavirus (HPV).
• The role of microRNA (miRNA) expression in TSCC, particularly concerning HPV status and genetic mutations, remains underexplored.
• Previous research focused on clinicopathological and genetic data, necessitating a deeper investigation into miRNA profiles.

Purpose of the Study:

• To profile miRNA expression in TSCC tissues in relation to HPV status.
• To identify potential diagnostic biomarkers and therapeutic targets for TSCC.
• To investigate the association between miRNA expression, HPV status, and the TERT promoter (TERTp) gene.

Main Methods:

• MicroRNA expression profiling was performed on 22 surgically resected TSCC tissues and matched normal tonsil tissues using the nCounter Nanostring miRNA Expression assay.
• Hierarchical clustering analysis was employed to identify differentially expressed miRNAs.
• Functional enrichment analysis was conducted to determine the biological roles of dysregulated miRNAs.

Main Results:

• The TERT promoter (TERTp) gene was identified as the sole relevant candidate gene linked to differentially expressed miRNAs in TSCC.
• A distinct miRNA expression signature was associated with HPV-positive TSCC, characterized by high levels of hsa-miR-1285-5p, hsa-miR-1203, hsa-miR-663a, hsa-miR-1303, hsa-miR-33a-5p, and hsa-miR-3615, and low levels of hsa-miR-3182, hsa-miR-219a-2-3p, and hsa-miR-767-3p (p = 0.009).
• Dysregulated miRNAs were primarily involved in protein binding and cellular component functions.

Conclusions:

• Specific miRNAs, notably hsa-miR-1285-5p and hsa-miR-663a, are significantly associated with HPV-positive TSCC, particularly those with TERTp mutations.
• These identified miRNAs hold promise as potential biomarkers for early TSCC detection.
• The findings suggest these miRNAs could be explored as novel therapeutic targets for HPV-positive TSCC.