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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1459572

Recombinant adenoviruses expressing HPV16/18 E7 upregulate the HDAC6 and DNMT3B genes in C33A cells

Provisionally accepted
Yunting Shao Yunting Shao 1Pir Tariq Shah Pir Tariq Shah 1Qisheng Su Qisheng Su 2SHANHU LI SHANHU LI 3Fang Huang Fang Huang 3Peng Wang Peng Wang 3Jun Wang Jun Wang 4Chengjun Wu Chengjun Wu 1*
  • 1 Faculty of Medicine, School of Basic Medical Sciences, Dalian University of Technology, Dalian, China, Dalian, China
  • 2 Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning Province, China
  • 3 Department of Cell Engineering, Beijing Institute of Biotechnology, Beijing, China
  • 4 Obstetrics and Gynecology department，the second affiliated hospital of Dalian Medical University Mailin, Dalian, China

The final, formatted version of the article will be published soon.

    Objective: High-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed. Methods: We used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer. Results: RNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer.The successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers.

    Keywords: high-risk HPV, Recombinant virus, E6/E7 gene, HDAC6, DNMT3B

    Received: 04 Jul 2024; Accepted: 05 Sep 2024.

    Copyright: © 2024 Shao, Shah, Su, LI, Huang, Wang, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chengjun Wu, Faculty of Medicine, School of Basic Medical Sciences, Dalian University of Technology, Dalian, China, Dalian, China

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