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OTUD1 chemosensitizes triple-negative breast cancer to doxorubicin by modulating P16 expression.
Zhou, Tao; Wu, Yihao; Qian, Da; Tang, Hongchao; Liu, Xiaozhen; Qiu, Jie; Wang, Danhong; Hong, Weimin; Meng, Xuli; Zheng, Qinghui.
Afiliación
  • Zhou T; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.
  • Wu Y; College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
  • Qian D; Department of Burn and Plastic Surgery-Hand Surgery, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu 215500, Jiangsu Province, China.
  • Tang H; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Key Laboratory for diagnosis and treatment of upper limb edema and stasis of breast cancer, Zhejiang Provincial People'
  • Liu X; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Key Laboratory for diagnosis and treatment of upper limb edema and stasis of breast cancer, Zhejiang Provincial People'
  • Qiu J; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.
  • Wang D; College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
  • Hong W; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.
  • Meng X; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Key Laboratory for diagnosis and treatment of upper limb edema and stasis of breast cancer, Zhejiang Provincial People'
  • Zheng Q; General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Key Laboratory for diagnosis and treatment of upper limb edema and stasis of breast cancer, Zhejiang Provincial People'
Pathol Res Pract ; 247: 154571, 2023 Jul.
Article en En | MEDLINE | ID: mdl-37257246
Chemotherapy remains a critical component of triple-negative breast cancer (TNBC) treatment; however, patients often develop resistance to chemotherapeutic agents. Accumulating evidence indicates that deubiquitylases (DUBs) play pivotal roles in regulating cell proliferation, differentiation, apoptosis, and tumorigenesis. Deubiquitylase OTUD1 is considered a tumor suppressor in various cancers, yet its role in doxorubicin sensitivity in breast cancer patients remains inadequately understood. In this study, we investigated the expression levels and prognostic role of OTUD1 in breast cancer. Our findings demonstrated that OTUD1 was downregulated in TNBC, and lower OTUD1 expression levels were correlated with poor prognosis. We utilized the CCK-8 cell viability assay, flow cytometric analysis, and a TNBC mouse xenograft model to examine the influence of OTUD1 on doxorubicin (DOX) chemotherapy sensitivity in vitro and in vivo. Western blot and immunohistochemistry were employed to explore the correlation between OTUD1 and P16. Our results indicated that upregulation of OTUD1 expression inhibits TNBC cell proliferation and enhances its sensitivity to doxorubicin. Additionally, rescue experiments confirmed that the chemosensitizing effect of OTUD1 overexpression could be reversed by the inhibition of P16. Therefore, our findings reveal that OTUD1 sensitizes TNBC cells to DOX by upregulating P16 expression, suggesting a potential new diagnostic biomarker and therapeutic target for the future treatment of TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania