miR-506: a regulator of chemo-sensitivity through suppression of the RAD51-homologous recombination axis

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• 作者：Guoyan Liu ; Fengxia Xue ; Wei Zhang
• 关键词：MicroRNA ; 506 ; Homologous recombination ; Drug sensitivity ; Synthetic lethality ; RAD51
• 刊名：Chinese Journal of Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：34
• 期：3
• 全文大小：818KB
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• 作者单位：Guoyan Liu (1)
  Fengxia Xue (1)
  Wei Zhang (2)
  
  1. Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, P.R. China
  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
  
• 刊物类别：Oncology;
• 刊物主题：Oncology;
• 出版者：BioMed Central
• ISSN：1944-446X

文摘

Ovarian carcinoma is the most lethal gynecologic malignancy. Resistance to platinum is considered the major problem affecting prognosis. Our recent study established that microRNA-506 (miR-506) expression was closely associated with progression-free survival and overall survival in two independent patient cohorts totaling 598 epithelial ovarian cancer cases. Further functional study demonstrated that miR-506 could augment the response to cisplatin and olaparib through targeting RAD51 and suppressing homologous recombination in a panel of ovarian cancer cell lines. Systemic delivery of miR-506 in an orthotopic ovarian cancer mouse model significantly augmented the cisplatin response, thus recapitulating the clinical observation. Therefore, miR-506 plays a functionally important role in homologous recombination and has important therapeutic value for sensitizing cancer cells to chemotherapy, especially in chemo-resistant patients with attenuated expression of miR-506. Keywords MicroRNA-506 Homologous recombination Drug sensitivity Synthetic lethality RAD51