Glucocorticoid regulation of a novel HPV–E6–p53–miR‐145 pathway modulates invasion and therapy resistance of cervical cancer cells

• DOI: 10.1002/path.3997
• Publication Date: 2012-01-27T22:37:13Z
• Authors: Ming Shi; Libin Du; Dan Liu; Lu Qian; Meiru Hu; Ming Yu; Zhengyan Yang; Mingzhen Zhao; Changguo Chen; Liang Guo; Lina Wang; Lun Song; Yuanfang Ma; Ning Guo
• Keywords: 0301 basic medicine; Hydrocortisone; Papillomavirus Infections; Anti-Inflammatory Agents; Down-Regulation; Apoptosis; Oncogene Proteins, Viral; Adenocarcinoma; Blotting, Northern; Flow Cytometry; Real-Time Polymerase Chain Reaction; Transfection; 3. Good health; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Drug Resistance, Neoplasm; Humans; Female; Tumor Suppressor Protein p53; Cell Migration Assays; HeLa Cells

Abstract Glucocorticoids are stress‐responsive neuroendocrine mediators and play an important role in malignant progression, especially solid tumours. We demonstrate a novel mechanism by which glucocorticoids modulate p53‐dependent miR‐145 expression HPV‐positive cervical cancer cells through induction of E6 proteins. found that was reduced tissues. Cortisol induced HPV‐E6 suppressed p53 cells. MiR‐145 wild‐type ‐dependent, cortisol‐induced down‐regulation prevented chemotherapy‐induced apoptosis, whereas over‐expression enhanced sensitivity to mitomycin reversed the chemoresistance glucocorticoids. also show augments effects suppressing inhibitors cells, suggesting plays tumour suppression. Finally, we inhibits both motility invasion Our findings identify pathway macroenvironment affects growth, therapy resistance may serve as target for therapy. Copyright © 2012 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.