Lin Kai-Ti, Yeh Yu-Ming, Chuang Chi-Mu, Yang Scarlett Y, Chang Jer-Wei, Sun Shu-Pin, Wang Yi-Shiang, Chao Kuan-Chong, Wang Lu-Hai
Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
1] Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, No. 201, Sector 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan [2] Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Nat Commun. 2015 Jan 8;6:5917. doi: 10.1038/ncomms6917.
Glucocorticoids are widely used in conjunction with chemotherapy for ovarian cancer to prevent hypersensitivity reactions. Here we reveal a novel role for glucocorticoids in the inhibition of ovarian cancer metastasis. Glucocorticoid treatments induce the expression of miR-708, leading to the suppression of Rap1B, which result in the reduction of integrin-mediated focal adhesion formation, inhibition of ovarian cancer cell migration/invasion and impaired abdominal metastasis in an orthotopic xenograft mouse model. Restoring Rap1B expression reverts glucocorticoid-miR-708 cascade-mediated suppression of ovarian cancer cell invasion and metastasis. Clinically, low miR-708 and high Rap1B are found in late-state ovarian tumours, as compared with normal, and patients with high miR-708 show significantly better survival. Overall, our findings reveal an opportunity for glucocorticoids and their downstream mediators, miR-708 or Rap1B, as therapeutic modalities against metastatic ovarian epithelial cancer.
糖皮质激素广泛用于与卵巢癌化疗联合使用，以预防过敏反应。在此，我们揭示了糖皮质激素在抑制卵巢癌转移中的新作用。糖皮质激素治疗可诱导miR-708的表达，导致Rap1B的抑制，这会导致整合素介导的粘着斑形成减少，抑制卵巢癌细胞迁移/侵袭，并在原位异种移植小鼠模型中损害腹部转移。恢复Rap1B表达可逆转糖皮质激素-miR-708级联介导的卵巢癌细胞侵袭和转移抑制。临床上，与正常情况相比，晚期卵巢肿瘤中miR-708低而Rap1B高，而miR-708高的患者生存率明显更高。总体而言，我们的研究结果揭示了糖皮质激素及其下游介质miR-708或Rap1B作为转移性卵巢上皮癌治疗方式的机会。
