Wu Yanju, Meng Shu, Zhao Haoqi, Tan Bowen, Gao Jinte, Du Jingyi, Meng Xiaona
Teaching Center for Basic Medical Experiment, China Medical University, Shenyang, 110122, Liaoning Province, People's Republic of China.
The Second Drug Room of Shenyang Institute for Food and Drug Control, Shenyang Institute for Food and Drug Control, Shenyang, 110122, Liaoning Province, People's Republic of China.
J Cancer Res Clin Oncol. 2025 Aug 27;151(8):236. doi: 10.1007/s00432-025-06290-y.
This research explores the prognostic value of DHRS9 in ovarian carcinoma and elucidates its regulatory mechanisms.
Bioinformatic analyses were applied to clarify the association between DHRS9 expression level and clinical survival outcomes in ovarian cancer patients. Functional assays were conducted to evaluate cell growth, migration, and invasion. Apoptosis was quantified via flow cytometry. The expression of Dehydrogenase/Reductase Member 9 (DHRS9) and sequestosome 1 (SQSTM1) at both mRNA and protein levels was analyzed via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Mass spectrometry identified SQSTM1 as a putative downstream effector of DHRS9, and their interaction was validated by co-immunoprecipitation (Co-IP). The in vivo effects of DHRS9 knockdown were examined in a subcutaneous xenograft tumor model of nude mice.
Bioinformatic analysis showed that elevated DHRS9 expression correlated with reduced overall survival in ovarian cancer patients. Silencing DHRS9 attenuated cell growth, migration, and invasion, whereas promoting apoptotic activity. In contrast, DHRS9 overexpression enhanced oncogenic behaviors and suppressed apoptosis. Mass spectrometry and Co-IP analyses confirmed SQSTM1 as an interacting partner of DHRS9, and knockdown of DHRS9 decreased SQSTM1 protein levels in vivo and in vitro, while its overexpression increased SQSTM1 levels. Moreover, functional studies demonstrated that SQSTM1 knockdown reduced ovarian cell growth, migration, and invasion. Xenograft experiments further demonstrated that DHRS9 knockdown resulted in decreased tumor volume.
DHRS9 promotes ovarian cancer proliferation, migration, and invasion, and inhibits apoptosis through its interaction with SQSTM1. These findings indicate that DHRS9 may serve as a potential prognostic indicator and therapeutic candidate in ovarian cancer.
本研究探讨脱氢酶/还原酶9（DHRS9）在卵巢癌中的预后价值，并阐明其调控机制。
应用生物信息学分析来明确DHRS9表达水平与卵巢癌患者临床生存结局之间的关联。进行功能试验以评估细胞生长、迁移和侵袭。通过流式细胞术对细胞凋亡进行定量分析。采用定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法分析DHRS9和聚集体蛋白1（SQSTM1）在mRNA和蛋白质水平的表达。质谱分析确定SQSTM1为DHRS9的潜在下游效应分子，并通过免疫共沉淀（Co-IP）验证它们之间的相互作用。在裸鼠皮下异种移植瘤模型中检测DHRS9敲低的体内效应。
生物信息学分析表明，DHRS9表达升高与卵巢癌患者总生存期缩短相关。沉默DHRS9可减弱细胞生长、迁移和侵袭，同时促进细胞凋亡活性。相反，DHRS9过表达增强致癌行为并抑制细胞凋亡。质谱分析和Co-IP分析证实SQSTM1是DHRS9的相互作用伴侣，敲低DHRS9可降低体内外SQSTM1蛋白水平，而过表达则增加SQSTM1水平。此外，功能研究表明，敲低SQSTM1可降低卵巢细胞的生长、迁移和侵袭。异种移植实验进一步证明，敲低DHRS9可导致肿瘤体积减小。
DHRS9通过与SQSTM1相互作用促进卵巢癌增殖、迁移和侵袭，并抑制细胞凋亡。这些发现表明，DHRS9可能作为卵巢癌潜在的预后指标和治疗靶点。
