A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma. (September 2017)

• Record Type: Journal Article
• Authors: Krishnan, Aswini R.; Zheng, Hao; Kwok, James G.; Qu, Yuanhao; Zou, Angela E.; Korrapati, Avinaash; Li, Pin Xue; Califano, Joseph A.; Hovell, Melbourne F.; Wang-Rodriguez, Jessica; Ongkeko, Weg M.
• Is Part Of: Oral oncology. Volume 72(2017)
• Page Start: 56
• Page End: 64
• Publication Date: 2017-09
• Subjects: HNSCC head and neck squamous cell carcinoma -- miRNA microRNA -- HPV human papillomavirus -- TCGA The Cancer Genome Atlas; Smoking -- Head and neck neoplasms -- RNA, Untranslated -- MicroRNAs; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2017.07.009
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: RNA-seq analysis implicated 170 microRNAs in smoking-induced HNSCC. Distinct panels of microRNAs correlated with tumor site, stage, and metastasis. 4 microRNAs associated with patient survival. In vitro treatment with cigarette smoke extract verified microRNA dysregulation. 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.