Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection

Nijiro Nohata; Martin C Abba; J Silvio Gutkind

doi:10.1016/j.oraloncology.2016.05.014

Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection

Oral Oncol. 2016 Aug:59:58-66. doi: 10.1016/j.oraloncology.2016.05.014.

Authors

Nijiro Nohata¹, Martin C Abba², J Silvio Gutkind³

Affiliations

¹ Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
² CINIBA, CONICET, School of Medical Sciences, National University of La Plata, La Plata, Argentina.
³ Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States; Department of Pharmacology, University of California, San Diego, La Jolla, CA, United States. Electronic address: sgutkind@ucsd.edu.

Abstract

Objectives: The role of long non-coding RNA (lncRNA) expression in human head and neck squamous cell carcinoma (HNSCC) is still poorly understood. In this study, we aimed at establishing the onco-lncRNAome profiling of HNSCC and to identify lncRNAs correlating with prognosis and patient survival.

Materials and methods: The Atlas of Noncoding RNAs in Cancer (TANRIC) database was employed to retrieve the lncRNA expression information generated from The Cancer Genome Atlas (TCGA) HNSCC RNA-sequencing data. RNA-sequencing data from HNSCC cell lines were also considered for this study. Bioinformatics approaches, such as differential gene expression analysis, survival analysis, principal component analysis, and Co-LncRNA enrichment analysis were performed.

Results: Using TCGA HNSCC RNA-sequencing data from 426 HNSCC and 42 adjacent normal tissues, we found 728 lncRNA transcripts significantly and differentially expressed in HNSCC. Among the 728 lncRNAs, 55 lncRNAs were significantly associated with poor prognosis, such as overall survival and/or disease-free survival. Next, we found 140 lncRNA transcripts significantly and differentially expressed between Human Papilloma Virus (HPV) positive tumors and HPV negative tumors. Thirty lncRNA transcripts were differentially expressed between TP53 mutated and TP53 wild type tumors. Co-LncRNA analysis suggested that protein-coding genes that are co-expressed with these deregulated lncRNAs might be involved in cancer associated molecular events. With consideration of differential expression of lncRNAs in a HNSCC cell lines panel (n=22), we found several lncRNAs that may represent potential targets for diagnosis, therapy and prevention of HNSCC.

Conclusion: LncRNAs profiling could provide novel insights into the potential mechanisms of HNSCC oncogenesis.

Keywords: Head and neck squamous cell carcinoma (HNSCC); Human papilloma virus (HPV); Long non-coding RNA; RNA-sequencing; TCGA; TP53.

Publication types

Review

MeSH terms

Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / virology
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / virology
Humans
Papillomavirus Infections / genetics*
RNA, Long Noncoding / genetics*

Substances

RNA, Long Noncoding

Abstract

Publication types

MeSH terms

Substances

Grants and funding