Cargando…

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

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 a...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Yan, Song, Yi, Du, Quan, Wang, Chi Chiu, Li, Hu, Sui, Yi, Zhang, Yuying, Tang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282752/
https://www.ncbi.nlm.nih.gov/pubmed/37350944
http://dx.doi.org/10.3389/fonc.2023.1175958
_version_ 1785061187667361792
author Deng, Yan
Song, Yi
Du, Quan
Wang, Chi Chiu
Li, Hu
Sui, Yi
Zhang, Yuying
Tang, Tao
author_facet Deng, Yan
Song, Yi
Du, Quan
Wang, Chi Chiu
Li, Hu
Sui, Yi
Zhang, Yuying
Tang, Tao
author_sort Deng, Yan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10282752
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-102827522023-06-22 Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12 Deng, Yan Song, Yi Du, Quan Wang, Chi Chiu Li, Hu Sui, Yi Zhang, Yuying Tang, Tao Front Oncol Oncology 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. Frontiers Media S.A. 2023-06-07 /pmc/articles/PMC10282752/ /pubmed/37350944 http://dx.doi.org/10.3389/fonc.2023.1175958 Text en Copyright © 2023 Deng, Song, Du, Wang, Li, Sui, Zhang and Tang https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Oncology
Deng, Yan
Song, Yi
Du, Quan
Wang, Chi Chiu
Li, Hu
Sui, Yi
Zhang, Yuying
Tang, Tao
Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title_full Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title_fullStr Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title_full_unstemmed Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title_short Anti-HPV16 oncoproteins siRNA therapy for cervical cancer using a novel transdermal peptide PKU12
title_sort anti-hpv16 oncoproteins sirna therapy for cervical cancer using a novel transdermal peptide pku12
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282752/
https://www.ncbi.nlm.nih.gov/pubmed/37350944
http://dx.doi.org/10.3389/fonc.2023.1175958
work_keys_str_mv AT dengyan antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT songyi antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT duquan antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT wangchichiu antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT lihu antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT suiyi antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT zhangyuying antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12
AT tangtao antihpv16oncoproteinssirnatherapyforcervicalcancerusinganoveltransdermalpeptidepku12