Long non-coding RNA FAM83H-AS1 is regulated by human papillomavirus 16 E6 independently of p53 in cervical cancer cells

Sci Rep. 2019 Mar 6;9(1):3662. doi: 10.1038/s41598-019-40094-8.

Abstract

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and head and neck cancers. The expression of the viral oncoproteins E6 and E7 are essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) have been found to be dysregulated in several cancers, suggesting an important role in tumorigenesis. In order to identify host lncRNAs affected by HPV infection, we expressed the high-risk HPV-16 E6 oncoprotein in primary human keratinocytes and measured the global lncRNA expression profile by high-throughput sequencing (RNA-seq). We found several host lncRNAs differentially expressed by E6 including GAS5, H19, and FAM83H-AS1. Interestingly, FAM83H-AS1 was found overexpressed in HPV-16 positive cervical cancer cell lines in an HPV-16 E6-dependent manner but independently of p53 regulation. Furthermore, FAM83H-AS1 was found to be regulated through the E6-p300 pathway. Knockdown of FAM83H-AS1 by siRNAs decreased cellular proliferation, migration and increased apoptosis. FAM83H-AS1 was also found to be altered in human cervical cancer tissues and high expression of this lncRNA was associated with worse overall survival, suggesting an important role in cervical carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / metabolism*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Infections / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*
  • Sequence Analysis, RNA
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology*

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • RNA, Long Noncoding
  • Repressor Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53