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. 2024 Jun 5:910:148321.
doi: 10.1016/j.gene.2024.148321. Epub 2024 Feb 28.

Identification of hub genes and potential therapeutic mechanisms related to HPV positive head and neck squamous carcinoma based on full transcriptomic detection and ceRNA network construction

Kunpeng Wang  1 , Tingting Zhang  1 , Xia Li  1 , Xinran Zhang  1 , Rui Li  2 , Boyu Pan  3 , Jiayin Deng  4
Affiliations

Identification of hub genes and potential therapeutic mechanisms related to HPV positive head and neck squamous carcinoma based on full transcriptomic detection and ceRNA network construction

Kunpeng Wang et al. Gene. .

Abstract

Infection with human papillomavirus (HPV) is a major risk factor for head and neck squamous cell carcinoma (HNSCC). The objective of this study is to investigate the gene expression profiles and signaling pathways that are specific to HPV-positive HNSCC (HPV+ HNSCC). Moreover, a competing endogenous RNA (ceRNA) network analysis was utilized to identify the core gene of HPV+ HNSCC and potential targeted therapeutic drugs. Transcriptome sequencing analysis identified 3,253 coding RNAs and 3,903 non-coding RNAs (ncRNAs) that exhibited preferentially expressed in HPV+ HNSCC. Four key signaling pathways were selected through pathway enrichment analysis. By combining ceRNA network and protein-protein interaction (PPI) network topology analysis, RNA Polymerase II Associated Protein 2 (RPAP2), which also exhibited high expression in HPV+ HNSCC based on the TCGA database, was identified as the hub gene. Gene set enrichment analysis (GSEA) results revealed RPAP2's involvement in various signaling pathways, encompassing basal transcription factors, ubiquitin-mediated proteolysis, adherens junction, other glycan degradation, ATP-binding cassette (ABC) transporters, and oglycan biosynthesis. Five potential small molecule targeted drugs (enzastaurin, brequinar, talinolol, phenylbutazone, and afuresertib) were identified using the cMAP database, with enzastaurin showing the highest affinity for RPAP2. Cellular functional experiments confirmed the inhibitory effect of enzastaurin on cell viability of HPV+ HNSCC and RPAP2 expression levels. Additionally, enzastaurin treatment suppressed the expression levels of the top-ranked long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) in the ceRNA network. This study based on the ceRNA network provides valuable insights into the molecular mechanisms and potential therapeutic strategies for HPV+ HNSCC, and provide theoretical basis for the exploration of HPV+ HNSCC biomarkers and the development of targeted drugs.

Keywords: Drug repurposing; HPV; Head and neck squamous carcinoma; Hub genes; ceRNA network.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kunpeng Wang reports financial support was provided by Tianjin Municipal Science and Technology Committee. Kunpeng Wang reports a relationship with Tianjin Municipal Science and Technology Committee that includes: funding grants. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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