title: Transcriptome sequencing uncovers novel long noncoding and small nucleolar RNAs dysregulated in head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma persists as one of the most common and deadly malignancies, with early detection and effective treatment still posing formidable challenges. To expand our currently sparse knowledge of the noncoding alterations involved in the disease and identify potential biomarkers and therapeutic targets, we globally profiled the dysregulation of small nucleolar and long noncoding RNAs in head and neck tumors. Using next-generation RNA-sequencing data from 40 pairs of tumor and matched normal tissues, we found 2808 long noncoding RNA (lncRNA) transcripts significantly differentially expressed by a fold change magnitude ≥2. Meanwhile, RNA-sequencing analysis of 31 tumor-normal pairs yielded 33 significantly dysregulated small nucleolar RNAs (snoRNA). In particular, we identified two dramatically down-regulated lncRNAs and one down-regulated snoRNA whose expression levels correlated significantly with overall patient survival, suggesting their functional significance and clinical relevance in head and neck cancer pathogenesis. We confirmed the dysregulation of these noncoding RNAs in head and neck cancer cell lines derived from different anatomic sites, and determined that ectopic expression of the two lncRNAs inhibited key EMT and stem cell genes and reduced cellular proliferation and migration. As a whole, noncoding RNAs are pervasively dysregulated in head and squamous cell carcinoma. The precise molecular roles of the three transcripts identified warrants further characterization, but our data suggest that they are likely to play substantial roles in head and neck cancer pathogenesis and are significantly associated with patient survival.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Zou
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jonjei
authors.initials: J
authors.lastname: Ku
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Honda
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Vicky
authors.initials: V
authors.lastname: Yu
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Selena Z
authors.initials: SZ
authors.lastname: Kuo
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Maarouf A
authors.initials: MA
authors.lastname: Saad
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hinton
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Brumund
authors.affiliation: Veterans Administration Medical Center and Department of Pathology, University of California, San Diego, La Jolla, California 92161, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Veterans Administration Medical Center and Department of Pathology, University of California, San Diego, La Jolla, California 92161, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang-Rodriguez
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Weg M
authors.initials: WM
authors.lastname: Ongkeko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*; D016019:Survival Analysis
chemical_list: D062085:RNA, Long Noncoding; D020537:RNA, Small Nucleolar
keywords: HNSCC; RNA-sequencing; long noncoding RNAs; small nucleolar RNAs