Aswini R Krishnan1, Hao Zheng2, James G Kwok3, Yuanhao Qu4, Angela E Zou5, Avinaash Korrapati6, Pin Xue Li7, Joseph A Califano8, Melbourne F Hovell9, Jessica Wang-Rodriguez10, Weg M Ongkeko11. 1. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: arkrishn@ucsd.edu. 2. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: h3zheng@ucsd.edu. 3. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: jak114@ucsd.edu. 4. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: yuq024@ucsd.edu. 5. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: azou@ucsd.edu. 6. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: akorrapa@ucsd.edu. 7. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: p4li@ucsd.edu. 8. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: jcalifano@ucsd.edu. 9. Graduate School of Public Health, San Diego State University, San Diego, CA, United States. Electronic address: mhovell@cbeachsdsu.org. 10. Veterans Administration Medical Center and Department of Pathology, University of California San Diego, La Jolla, CA, United States. Electronic address: jessica.wang-rodriguez@va.gov. 11. Department of Otolaryngology - Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: wongkeko@ucsd.edu.
Abstract
OBJECTIVE: While tobacco smoking is a well-known risk factor for head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying tobacco-induced HNSCC remain unclear. This study sought to comprehensively identify microRNA (miRNA) alterations and evaluate their clinical relevance in smoking-induced HNSCC pathogenesis and progression. MATERIALS AND METHODS: Using small RNA-sequencing data and clinical data from 145 HNSCC patients, we performed a series of differential expression and correlation analyses to identify a panel of tobacco-dysregulated miRNAs associated with key clinical characteristics in HNSCC. We then examined the expression patterns of these miRNAs in normal epithelial cell lines following exposure to cigarette smoke extract. RESULTS: Our analyses revealed distinct panels of miRNAs to be dysregulated with smoking status and associated with additional clinical features, including tumor stage, metastasis, anatomic site, and patient survival. The differential expression of key miRNAs, including miR-101, miR-181b, miR-486, and miR-1301, was verified in cigarette-treated epithelial cell lines, suggesting their potential roles in the early development of smoking-related HNSCCs. CONCLUSION: Specific alterations in miRNA expression may be traced to tobacco use and are associated with important HNSCC clinical characteristics. Future studies of these miRNAs may be valuable for furthering the understanding and targeted treatment of smoking-associated HNSCC.
OBJECTIVE: While tobacco smoking is a well-known risk factor for head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying tobacco-induced HNSCC remain unclear. This study sought to comprehensively identify microRNA (miRNA) alterations and evaluate their clinical relevance in smoking-induced HNSCC pathogenesis and progression. MATERIALS AND METHODS: Using small RNA-sequencing data and clinical data from 145 HNSCC patients, we performed a series of differential expression and correlation analyses to identify a panel of tobacco-dysregulated miRNAs associated with key clinical characteristics in HNSCC. We then examined the expression patterns of these miRNAs in normal epithelial cell lines following exposure to cigarette smoke extract. RESULTS: Our analyses revealed distinct panels of miRNAs to be dysregulated with smoking status and associated with additional clinical features, including tumor stage, metastasis, anatomic site, and patient survival. The differential expression of key miRNAs, including miR-101, miR-181b, miR-486, and miR-1301, was verified in cigarette-treated epithelial cell lines, suggesting their potential roles in the early development of smoking-related HNSCCs. CONCLUSION: Specific alterations in miRNA expression may be traced to tobacco use and are associated with important HNSCC clinical characteristics. Future studies of these miRNAs may be valuable for furthering the understanding and targeted treatment of smoking-associated HNSCC.
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