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Let-7e Suppresses DNA Damage Repair and Sensitizes Ovarian Cancer to Cisplatin through Targeting PARP1.
Xiao, Man; Guo, Jianfeng; Xie, Lisha; Yang, Chun; Gong, Lanqing; Wang, Zehua; Cai, Jing.
Afiliación
  • Xiao M; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Guo J; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Xie L; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yang C; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Gong L; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang Z; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. caijingmmm@hotmail.com zehuawang@163.net.
  • Cai J; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. caijingmmm@hotmail.com zehuawang@163.net.
Mol Cancer Res ; 18(3): 436-447, 2020 03.
Article en En | MEDLINE | ID: mdl-31722968
Increased DNA damage repair is one of the mechanisms implicated in cisplatin resistance. Our previous study indicated that the deregulation of let-7e promoted cisplatin resistance and that let-7e could suppress DNA double-strand break repair in ovarian cancer. In this study, we further characterized the role of let-7e in DNA damage repair and cisplatin resistance in ovarian cancer, and investigated the underlying mechanisms. The alkaline and neutral comet assay indicated that let-7e impeded both DNA single- and double-strand break repairs through downregulating its target gene PARP1. In vitro and in vivo experiments provided evidence that the let-7e-PARP1-DNA repair axis was involved in the modulation of cisplatin sensitivity in ovarian cancer. Contrary to let-7e, PARP1 was overexpressed in cisplatin-resistant ovarian cancer tissues, and patients with high PARP1 expression exhibited poor progression-free survival (PFS) and overall survival (OS). Multivariate logistic and Cox regression analyses showed that let-7e and FIGO stage were independent prognostic factors for PFS and OS, whereas let-7e and PARP1 were able to independently predict chemotherapy response. Taken together, our results indicated that low expression of let-7e promoted DNA single- and double-strand break repairs and subsequently contributed to cisplatin resistance by relieving the suppression on PARP1 in ovarian cancer. IMPLICATIONS: Targeting the let-7e-PARP1-DNA repair axis might be an effective strategy for the treatment of chemoresistant ovarian cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Daño del ADN / Cisplatino / MicroARNs / Reparación del ADN / Poli(ADP-Ribosa) Polimerasa-1 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Daño del ADN / Cisplatino / MicroARNs / Reparación del ADN / Poli(ADP-Ribosa) Polimerasa-1 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos