title: Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B.
abstract: 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.
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Kai-Ti
authors.initials: KT
authors.lastname: Lin
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Yeh
authors.affiliation: 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.
authors.forename: Chi-Mu
authors.initials: CM
authors.lastname: Chuang
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Scarlett Y
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Jer-Wei
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Sun
authors.affiliation: 1] Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan [2] Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu 30013, Taiwan.
authors.forename: Yi-Shiang
authors.initials: YS
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, No. 201, Sector 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan.
authors.forename: Kuan-Chong
authors.initials: KC
authors.lastname: Chao
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli Country 350, Taiwan.
authors.forename: Lu-Hai
authors.initials: LH
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D064593:Heterografts / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008156:Luciferases; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; C568528:MIRN708 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; C116753:RAP1B protein, human; D020668:rap GTP-Binding Proteins