The lncRNA and miRNA regulatory axis in HPV16-positive oropharyngeal cancers

Dayna Sais; Meredith Hill; Fiona Deutsch; Phuong Thao Nguyen; Valerie Gay; Nham Tran

doi:10.1016/j.virol.2024.110220

The lncRNA and miRNA regulatory axis in HPV16-positive oropharyngeal cancers

Virology. 2024 Dec:600:110220. doi: 10.1016/j.virol.2024.110220. Epub 2024 Sep 5.

Authors

Dayna Sais¹, Meredith Hill², Fiona Deutsch³, Phuong Thao Nguyen⁴, Valerie Gay⁵, Nham Tran⁶

Affiliations

¹ School of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, Australia. Electronic address: [email protected].
² Graduate School of Biomedical Engineering, University of New South Wales, Australia.
³ School of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, Australia.
⁴ Transdisciplinary School, The University of Technology Sydney, Australia.
⁵ School of Electrical and Data Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, Australia.
⁶ School of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, Australia. Electronic address: [email protected].

PMID: 39244802
DOI: 10.1016/j.virol.2024.110220

Abstract

The global rise of oropharyngeal cancers (OPC) associated with the human papillomavirus (HPV) type 16 necessitates a deeper understanding of their underlying molecular mechanisms. Our study utilised RNA-sequencing data from The Cancer Genome Atlas (TCGA) to identify and analyse differentially expressed (DE) long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in HPV16-positive OPC, and to elucidate the interplay within the lncRNA/miRNA/mRNA regulatory network. We revealed 1929 DE lncRNAs and identified a significant expression shift in 37 of these, suggesting a regulatory 'sponge' function for miRNAs that modulate cellular processes. Notably, the lncRNA Linc00911 exhibited decreased expression in HPV16-positive OPC, a change directly attributable to HPV oncogenes E6 and E7 as confirmed by RT-qPCR in cell lines and patient samples. Our comprehensive analysis presents an expansive landscape of ncRNA-mRNA interactions, offering a resource for the ongoing pursuit of elucidating the molecular underpinnings of HPV-driven OPC.

Keywords: Human papillomavirus (HPV) type 16; Long ncRNAs; Oropharyngeal cancer (OPC); RNA regulation; microRNA and messenger RNA interactomes.

MeSH terms

Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Human papillomavirus 16* / genetics
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
Oncogene Proteins, Viral* / genetics
Oncogene Proteins, Viral* / metabolism
Oropharyngeal Neoplasms* / genetics
Oropharyngeal Neoplasms* / virology
Papillomavirus E7 Proteins / genetics
Papillomavirus E7 Proteins / metabolism
Papillomavirus Infections* / genetics
Papillomavirus Infections* / virology
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism

Substances

RNA, Long Noncoding
MicroRNAs
Oncogene Proteins, Viral
RNA, Messenger
Papillomavirus E7 Proteins
E6 protein, Human papillomavirus type 16
oncogene protein E7, Human papillomavirus type 16
Repressor Proteins