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

Oncogene volume 39, pages 862–876 (2020)Cite this article

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Abstract

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.

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Microarray data have been deposited in GEO database (accession number: GSE135469).

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Acknowledgements

We are grateful for providing the services from the RNAi Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Taiwan. RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center, Academia Sinica, Taiwan. This study was supported by grants MOST 107-2314-B-006-068-MY3, MOST 108-2314-B-006-004, MOST 108-2321-B-006-010, and MOST 106-2314-B-006-015-MY2 from the Ministry of Science and Technology, Taiwan.

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  1. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chia-Hao Tung, Yao-Tsung Tsai & Jia-En Wu

  2. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Li-Wei Kuo, Meng-Fan Huang, Keng-Fu Hsu & Tse-Ming Hong

  3. Clinical Medicine Research Center, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan

    Yi-Ying Wu & Tse-Ming Hong

  4. Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Keng-Fu Hsu

  5. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yuh-Ling Chen

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Tung, CH., Kuo, LW., Huang, MF. et al. MicroRNA-150-5p promotes cell motility by inhibiting c-Myb-mediated Slug suppression and is a prognostic biomarker for recurrent ovarian cancer. Oncogene 39, 862–876 (2020). https://doi.org/10.1038/s41388-019-1025-x

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