MicroRNA-150-5p promotes cell motility by inhibiting c-Myb-mediated Slug suppression and is a prognostic biomarker for recurrent ovarian cancer

• Published in: Oncogene Vol. 39; no. 4; pp. 862 - 876
• Main Authors: Tung, Chia-Hao, Kuo, Li-Wei, Huang, Meng-Fan, Wu, Yi-Ying, Tsai, Yao-Tsung, Wu, Jia-En, Hsu, Keng-Fu, Chen, Yuh-Ling, Hong, Tse-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.01.2020; Nature Publishing Group
• Subjects: 38/61; 38/89; 631/67/1517/1709; 631/67/322; 64/60; 82/1; 82/80; Adult; Aged; Apoptosis; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; c-Met protein; c-Myb protein; Cancer; Care and treatment; Cell Biology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Databases, Genetic; Diseases; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Human Genetics; Humans; Internal Medicine; Medical colleges; Medicine; Medicine & Public Health; Mesenchyme; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Oncology; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Peritoneal fluid; Peritoneum; Phenotypes; Prognosis; Proto-Oncogene Proteins c-myb - genetics; Proto-Oncogene Proteins c-myb - metabolism; Relapse; Scientific equipment and supplies industry; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Stem cells; Survival Rate; Up-Regulation; United States; Taiwan
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-019-1025-x

Treatment of ovarian cancer (OvCa) remains challenging owing to its high recurrence rates. Detachment of cancer cells into the peritoneal fluid plays a key role in OvCa relapse, but how this occurs remains incompletely understood. Here we examined global miRNA expression profiles of paired primary/recurrent OvCa specimens and identified a novel biomarker, microRNA-150-5p (miR-150-5p), that was significantly upregulated in 16 recurrent OvCa tissues compared with their matched primary specimens. Analyses of cohorts from two other groups confirmed that expression of miR-150-5p was associated with early relapse and poor survival of OvCa patients. Inhibition of miR-150-5p significantly inhibited the migration and invasion of OvCa cells and induced a mesenchymal-epithelial transition (MET) phenotype. We demonstrated that the proto-oncogene, MYB , is an miR-150-5p target in OvCa cells and that the miR-150-5p/c-Myb/Slug axis plays important roles in regulating epithelial-mesenchymal transition (EMT) in OvCa cells. Expression of MYB was significantly correlated with good clinical outcome in OvCa and was negatively correlated with Slug expression in late-stage clinical specimens. These results suggest that miR-150-5p upregulation mediates the progression of recurrent OvCa by targeting the c-Myb/Slug pathway. Inhibition of miR-150-5p may serve as a new therapeutic strategy for preventing recurrence of OvCa.