Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12

Frontiers in Oncology

Oncology

Hu Li¹  Yi Sui²  Yi Song³  Yan Deng³  Tao Tang⁴  Chi Chiu Wang⁵  Yuying Zhang⁶  Quan Du⁷ 

[1] Department of Gynecology, Pan Yu Central Hospital, Guangzhou, China;Cancer Institute, Panyu Central Hospital, Guangzhou, China;Department of Nutrition, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Department of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Department of Gynecology, Pan Yu Central Hospital, Guangzhou, China;Department of Obstetrics and Gynaecology, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China;Department of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Li Ka Shing Institute of Health Science, and School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China;Department of Obstetrics and Gynaecology, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China;The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China;

关键词: transdermal peptide;    HPV;    siRNA;    cervical cancer;    RNA-sequencing;    signaling pathway;   

DOI  :  10.3389/fonc.2023.1175958

 received in 2023-02-28, accepted in 2023-05-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

In this study, an innovative transdermal peptide, #PKU12, was developed based on transdermal peptide TD-1, and the anti-tumor effect of PKU12-based siRNA against HPV was investigated in vivo. Furthermore, transcriptome differences between PKU12 + siRNA treatment and control groups were compared to assess treatment effects. The top five upregulated and downregulated genes identified by RNA sequencing were further subjected to survival analysis. The present study, for the first time, showed that this novel peptide could enhance the transdermal delivery of the siRNA targeting HPV16 L1, E6, and E7. PKU12-based siRNA delivery significantly repressed the mRNA expression levels of HPV16 L1, E6, and E7 in the SiHa xenograft tumors and attenuated tumor growth as well. The RNA-sequencing results showed that a total of 586 DEGs were detected in the PKU12 + siRNA-treated tumor tissues compared to the control tumor tissues. The GSEA analysis revealed that DEGs were inversely associated with the HIF-1 signaling pathway, the TNF signaling pathway, the AGE-RAGE signaling pathway, the NF-kappa B signaling pathway, ferroptosis, the IL-17 signaling pathway, ovarian steroidogenesis, and rheumatoid arthritis. Further functional enrichment analysis revealed that DEGs were significantly enriched in several key pathways, including cytokine–cytokine receptor interaction, the TNF signaling pathway, and the IL-17 signaling pathway. High expression of MYH1, MYH4, FGG, DEPP1, and ZBTB16 was associated with shorter overall survival of patients with cervical cancer; high expression of SULT1E1, RAB3C, CXCR3, and PROX2 was associated with longer overall survival of patients with cervical cancer. In conclusion, the transdermal peptide PKU12 is potentially a good candidate for a siRNA delivery vehicle for the treatment of cervical cancer.

【 授权许可】

Unknown   
Copyright © 2023 Deng, Song, Du, Wang, Li, Sui, Zhang and Tang