DHRS9 promotes malignant progression of ovarian cancer through SQSTM1

• Published in: Journal of cancer research and clinical oncology Vol. 151; no. 8; pp. 236 - 11
• Main Authors: Wu, Yanju, Meng, Shu, Zhao, Haoqi, Tan, Bowen, Gao, Jinte, Du, Jingyi, Meng, Xiaona
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 27.08.2025; Springer Nature B.V; Springer
• Subjects: Antibodies; Apoptosis; Cancer Research; Cancer therapies; Cell growth; Cell migration; DHRS9; Flow cytometry; Hematology; Immunoprecipitation; Internal Medicine; Mass spectroscopy; Medical prognosis; Medicine; Medicine & Public Health; Membranes; mRNA; Oncology; Ovarian cancer; Ovarian carcinoma; Polymerase chain reaction; Proteins; Reagents; Software; SQSTM1; Statistical analysis; Tumor progression; Tumors; Variance analysis; Xenografts; United States > US; China; Japan; DHRS9; SQSTM1; Tumor progression; Apoptosis; Ovarian cancer
• ISSN: 1432-1335; 0171-5216; 1432-1335
• DOI: 10.1007/s00432-025-06290-y

Objective This research explores the prognostic value of DHRS9 in ovarian carcinoma and elucidates its regulatory mechanisms. Methods 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. Results 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. Conclusion 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.