Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25569036.
- Also identified by DOI 10.1038/ncomms6917 and PMC identifier 4354140.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Gene Expression Regulation, Neoplastic
- Glucocorticoids
- Heterografts
- MicroRNAs
- Neoplasm Metastasis
- Ovarian Neoplasms
- rap GTP-Binding Proteins