Hsa_Circ_0000615-Encoded 250-Amino Acid Polypeptide Suppresses Epithelial Ovarian Cancer Progression via Promoting HMGB1 Nuclear Accumulation
7 affiliations
- 1Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China
- 2Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- 3Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
- 4Department of Pathology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 5Gynecology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China
- 6Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China
- 7Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Shanghai, China
Abstract
Objectives: Circular RNAs (circRNAs) can encode functional peptides to regulate tumor progression, yet the roles of circRNA-encoded peptides in epithelial ovarian cancer (EOC) remain poorly understood. This study aimed to investigate the function of hsa_circ_0000615 (circ_0615) and its encoded polypeptide in EOC and explore its potential pre-clinical value as a candidate therapeutic target. Methods: We detected circ_0615 expression in EOC clinical tissues and cell lines. In vitro functional assays, in vivo xenograft and Patient-derived xenograft (PDX) models with adeno-associated virus (AAV)-mediated overexpression were used to assess tumor-suppressive phenotypes. Mass spectrometry, co-immunoprecipitation, western blotting, immunofluorescence, and chromatin immunoprecipitation were applied to characterize the circ_0615-encoded polypeptide Zinc Finger Protein 609-250-amino acid (ZNF609-250aa) and its interaction with high-mobility group box 1 (HMGB1). Results: circ_0615 was downregulated in EOC tissues and cell lines. Circ_0615 overexpression suppressed EOC proliferation and migration in vitro and in vivo. Mechanistically, circ_0615 promoted translation of ZNF609-250aa via eukaryotic translation initiation factor 2 subunit 1 (eIF2α). ZNF609-250aa bound HMGB1, reduced its ubiquitination, and promoted HMGB1 nuclear accumulation, which may contribute to repression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) transcription. AAV2/8-ZNF609-250aa restrained tumor growth in PDX models. Conclusion: Circ_0615-encoded ZNF609-250aa acts as a tumor suppressor in EOC, partially through modulating ZNF609-250aa-HMGB1-related molecular events. This study provides novel mechanistic insights and promising pre-clinical candidate targets requiring further validation for EOC intervention.
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BibTeX
@article{guo2026hsacirc0000615encoded,
title = {{Hsa_Circ_0000615-Encoded 250-Amino Acid Polypeptide Suppresses Epithelial Ovarian Cancer Progression via Promoting HMGB1 Nuclear Accumulation}},
author = {Ziyi Guo and Siyun Deng and Jiao Meng and Xiaofei Zhang and Yueyou Wang and Jiami Huang and Tonglu Li and Min Liu and Henghui Yang and Fangzhou Chen and Yuan Wang and Wei Meng and Shaojia Wang and Yanli Li},
journal = {Oncology Research},
year = {2026},
month = oct,
doi = {10.32604/or.2026.087931},
url = {https://doi.org/10.32604/or.2026.087931},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hsa_Circ_0000615-Encoded 250-Amino Acid Polypeptide Suppresses Epithelial Ovarian Cancer Progression via Promoting HMGB1 Nuclear Accumulation
AU - Ziyi Guo
AU - Siyun Deng
AU - Jiao Meng
AU - Xiaofei Zhang
AU - Yueyou Wang
AU - Jiami Huang
AU - Tonglu Li
AU - Min Liu
AU - Henghui Yang
AU - Fangzhou Chen
AU - Yuan Wang
AU - Wei Meng
AU - Shaojia Wang
AU - Yanli Li
PY - 2026
DA - 2026/10/28
JO - Oncology Research
DO - 10.32604/or.2026.087931
UR - https://doi.org/10.32604/or.2026.087931
AB - Objectives: Circular RNAs (circRNAs) can encode functional peptides to regulate tumor progression, yet the roles of circRNA-encoded peptides in epithelial ovarian cancer (EOC) remain poorly understood. This study aimed to investigate the function of hsa_circ_0000615 (circ_0615) and its encoded polypeptide in EOC and explore its potential pre-clinical value as a candidate therapeutic target. Methods: We detected circ_0615 expression in EOC clinical tissues and cell lines. In vitro functional assays, in vivo xenograft and Patient-derived xenograft (PDX) models with adeno-associated virus (AAV)-mediated overexpression were used to assess tumor-suppressive phenotypes. Mass spectrometry, co-immunoprecipitation, western blotting, immunofluorescence, and chromatin immunoprecipitation were applied to characterize the circ_0615-encoded polypeptide Zinc Finger Protein 609-250-amino acid (ZNF609-250aa) and its interaction with high-mobility group box 1 (HMGB1). Results: circ_0615 was downregulated in EOC tissues and cell lines. Circ_0615 overexpression suppressed EOC proliferation and migration in vitro and in vivo. Mechanistically, circ_0615 promoted translation of ZNF609-250aa via eukaryotic translation initiation factor 2 subunit 1 (eIF2α). ZNF609-250aa bound HMGB1, reduced its ubiquitination, and promoted HMGB1 nuclear accumulation, which may contribute to repression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) transcription. AAV2/8-ZNF609-250aa restrained tumor growth in PDX models. Conclusion: Circ_0615-encoded ZNF609-250aa acts as a tumor suppressor in EOC, partially through modulating ZNF609-250aa-HMGB1-related molecular events. This study provides novel mechanistic insights and promising pre-clinical candidate targets requiring further validation for EOC intervention.
SN - 0965-0407
SN - 1555-3906
ER -