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Computational methods reveal novel functionalities of PIWI-interacting RNAs in human papillomavirus-induced head and neck squamous cell carcinoma.
Krishnan, Aswini R; Qu, Yuanhao; Li, Pin Xue; Zou, Angela E; Califano, Joseph A; Wang-Rodriguez, Jessica; Ongkeko, Weg M.
Afiliação
  • Krishnan AR; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
  • Qu Y; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
  • Li PX; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
  • Zou AE; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
  • Califano JA; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
  • Wang-Rodriguez J; Veterans Administration San Diego Healthcare System and Department of Pathology, University of California San Diego, La Jolla, California, USA.
  • Ongkeko WM; Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
Oncotarget ; 9(4): 4614-4624, 2018 Jan 12.
Article em En | MEDLINE | ID: mdl-29435129
Human papillomavirus (HPV) infection is the fastest growing cause of head and neck squamous cell carcinoma (HNSCC) today, but its role in malignant transformation remains unclear. This study aimed to conduct a comprehensive investigation of PIWI-interacting RNA (piRNA) alterations and functionalities in HPV-induced HNSCC. Using 77 RNA-sequencing datasets from TCGA, we examined differential expression of piRNAs between HPV16(+) HNSCC and HPV(-) Normal samples, identifying a panel of 30 HPV-dysregulated piRNAs. We then computationally investigated the potential mechanistic significances of these transcripts in HPV-induced HNSCC, identifying our panel of piRNAs to associate with the protein PIWIL4 as well as the RTL family of retrotransposon-like genes, possibly through direct binding interactions. We also recognized several HPV-dysregulated transcripts for their correlations with well-documented mutations and copy number variations in HNSCC as well as HNSCC clinical variables, demonstrating the potential ability of our piRNAs to play important roles in large-scale modulation of HNSCC in addition to their direct, smaller-scale interactions in this malignancy. The differential expression of key piRNAs, including NONHSAT077364, NONHSAT102574, and NONHSAT128479, was verified in vitro by evaluating endogenous expression in HPV(+) cancer vs. HPV(-) normal cell lines. Overall, our novel study provides a rigorous investigation of piRNA dysregulation in HPV-related HNSCC, and lends critical insight into the idea that these small regulatory transcripts may play crucial and previously unidentified roles in tumor pathogenesis and progression.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article