RPPH1 drives ovarian cancer cells proliferation via CDK9-c-Myc axis
- 1Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children’s Hospital of Chongqing Medical University), Chongqing, China
- 2Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- 3College of Basic Medicine, Chongqing Medical University, Chongqing, China
Abstract
Background: Dysregulation of the proto-oncogene c-Myc is a critical driver of ovarian cancer progression, yet the mechanisms governing its expression remain incompletely characterized.
Methods: A systematic bioinformatic analysis was used to screen long non-coding RNA involved in the regulation of c-Myc transcriptional activity in ovarian cancer without MYC amplification. The functions of RPPH1 were investigated using loss-of-function and gain-of-function strategies in vitro and in vivo. The therapeutic potential of targeting this axis was evaluated using the CDK9 inhibitor Atuveciclib, alone and in combined with cisplatin, in ovarian cancer xenograft models.
Results: RPPH1 expression correlated with c-Myc activity was upregulated in ovarian cancer. High RPPH1 levels predicted worse prognosis. Mechanistically, RPPH1 directly bound CDK9, enhancing its stability and promoting phosphorylation of c-Myc at Ser62. This modification prolongs c-Myc’s half-life and amplifies its transcriptional activity. Atuveciclib abrogated RPPH1-driven c-Myc stabilization and activity, while combination therapy with cisplatin synergistically suppressed RPPH1-high tumour growth in xenograft models.
Conclusions: We delineate a non-canonical RPPH1-CDK9-c-Myc axis governing oncoprotein stabilization in ovarian cancer, providing mechanistic insights into lncRNA-mediated post-translational regulation. CDK9 represents a therapeutic target for c-Myc-driven tumours, particularly RPPH1-overexpressing, cisplatin-resistant cases without MYC amplification. The combination of cisplatin and CDK9 inhibitor offers a promising translational strategy.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13048-026-02225-4.
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BibTeX
@article{chen2026rpph1,
title = {{RPPH1 drives ovarian cancer cells proliferation via CDK9-c-Myc axis}},
author = {Yue Chen and Li Tang and Haodong Huang and Yong Zhu and Yugang Chi and Yanzhou Wang and Xiongwei Cai},
journal = {Journal of Ovarian Research},
year = {2026},
month = aug,
doi = {10.1186/s13048-026-02225-4},
url = {https://doi.org/10.1186/s13048-026-02225-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - RPPH1 drives ovarian cancer cells proliferation via CDK9-c-Myc axis
AU - Yue Chen
AU - Li Tang
AU - Haodong Huang
AU - Yong Zhu
AU - Yugang Chi
AU - Yanzhou Wang
AU - Xiongwei Cai
PY - 2026
DA - 2026/08/07
JO - Journal of Ovarian Research
DO - 10.1186/s13048-026-02225-4
UR - https://doi.org/10.1186/s13048-026-02225-4
AB - Background: Dysregulation of the proto-oncogene c-Myc is a critical driver of ovarian cancer progression, yet the mechanisms governing its expression remain incompletely characterized. Methods: A systematic bioinformatic analysis was used to screen long non-coding RNA involved in the regulation of c-Myc transcriptional activity in ovarian cancer without MYC amplification. The functions of RPPH1 were investigated using loss-of-function and gain-of-function strategies in vitro and in vivo. The therapeutic potential of targeting this axis was evaluated using the CDK9 inhibitor Atuveciclib, alone and in combined with cisplatin, in ovarian cancer xenograft models. Results: RPPH1 expression correlated with c-Myc activity was upregulated in ovarian cancer. High RPPH1 levels predicted worse prognosis. Mechanistically, RPPH1 directly bound CDK9, enhancing its stability and promoting phosphorylation of c-Myc at Ser62. This modification prolongs c-Myc’s half-life and amplifies its transcriptional activity. Atuveciclib abrogated RPPH1-driven c-Myc stabilization and activity, while combination therapy with cisplatin synergistically suppressed RPPH1-high tumour growth in xenograft models. Conclusions: We delineate a non-canonical RPPH1-CDK9-c-Myc axis governing oncoprotein stabilization in ovarian cancer, providing mechanistic insights into lncRNA-mediated post-translational regulation. CDK9 represents a therapeutic target for c-Myc-driven tumours, particularly RPPH1-overexpressing, cisplatin-resistant cases without MYC amplification. The combination of cisplatin and CDK9 inhibitor offers a promising translational strategy. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13048-026-02225-4.
SN - 1757-2215
ER -