Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model

Mengqi Liu; Yuandong Luo; Xinyi Song; Rongmi Mo; Jiawei Fu; Quanlan Fu; Junjie Li; Jinyi Wu; Hongyin Wu; Furong Zhong; Hejie Li; Xiaosong Liu; Guoying Ni; Tianfang Wang

doi:10.1038/s41598-025-12450-4

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Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model

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Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model

Mengqi Liu, Yuandong Luo, Xinyi Song, Rongmi Mo, Jiawei Fu, Quanlan Fu, Junjie Li, Jinyi Wu, Hongyin Wu, Furong Zhong, …

Scientific Reports, Vol.15, pp.1-17

2025

DOI: https://doi.org/10.1038/s41598-025-12450-4

PMCID: PMC12311210

PMID: 40738927

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Abstract

KHDRBS1

caerin peptide

pyroptosis

IL-18

HeLa cell

cervical cancer

Cervical cancer remains a significant global health challenge, particularly in developing countries where access to HPV vaccination is limited. We previously demonstrated that caerin 1.1/1.9 (F1F3) peptides inhibit tumour growth in vitro and in vivo by inducing pyroptosis, followed by apoptosis and immune activation. In this study, we elucidate the molecular mechanisms underlying F1F3-induced pyroptosis in HeLa cells. Our results show that F1F3 triggers pyroptosis independently of GSDME, as evidenced by comparable IL-18 and LDH release in both wild type and GSDME knockout cells. Cross-linking mass spectrometry identified the interaction of F1 to KHDRBS1 and F3 to DDX5, respectively. Knockout of either KHDRBS1 or DDX5 enhanced HeLa cell sensitivity to F1F3 and significantly elevated IL-18 secretion. Notably, KHDRBS1-deficint tumours displayed accelerated growth yet responded more robustly to F1F3 treatment, suggesting a context-dependent tumour-suppressive role of KHDRBS1. These findings uncover a previously uncharacterised pathway regulated by KHDRBS1-DDX5 and demonstrate that F1F3 can effectively interfere with this axis to induce anti-tumour immune responses, highlighting their potential as novel therapeutic agents for cervical cancer.

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Title: Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model
Authors: Mengqi Liu - Guizhou University
Yuandong Luo - Zhongao Bio-pharmaceutical Technology Co., Ltd. (China)
Xinyi Song - Guangdong Pharmaceutical University
Rongmi Mo - Guangdong Pharmaceutical University
Jiawei Fu - Guangdong Pharmaceutical University
Quanlan Fu - Zhongao Bio-pharmaceutical Technology Co., Ltd. (China)
Junjie Li - Zhongao Bio-pharmaceutical Technology Co., Ltd. (China)
Jinyi Wu - Guangdong Pharmaceutical University
Hongyin Wu - Guangdong Pharmaceutical University
Furong Zhong - Guangdong Pharmaceutical University
Hejie Li - University of the Sunshine Coast, Queensland, Centre for Bioinnovation
Xiaosong Liu (Corresponding Author) - First People's Hospital of Foshan
Guoying Ni (Corresponding Author) - First People's Hospital of Foshan
Tianfang Wang (Corresponding Author) - University of the Sunshine Coast, Queensland, Centre for Bioinnovation
Publication details: Scientific Reports, Vol.15, pp.1-17
Publisher: Nature Publishing Group
Date published: 2025
DOI: 10.1038/s41598-025-12450-4
ISSN: 2045-2322
PMID: 40738927; PMC12311210
Copyright note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Data Availability: Data is provided within the manuscript or supplementary information files.
Grant note: This study was supported in part by National Natural Science Foundation of China (31971355), National Science Foundation of Guangdong province (2020A1515010855), and Deng Feng project of Foshan First People’s Hospital (2019A008).
Organisation Unit: School of Science and Engineering - Legacy; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 991149339902621
Output Type: Journal article

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