MicroRNA-150-5p promotes cell motility by inhibiting c-Myb-mediated Slug suppression and is a prognostic biomarker for recurrent ovarian cancer
MicroRNA-150-5p promotes cell motility by inhibiting c-Myb-mediated Slug suppression and is a prognostic biomarker for recurrent ovarian cancer
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DOI：
10.1038/s41388-019-1025-x
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发表时间：
2020-01-01
期刊：
影响因子：
8
通讯作者：
Hong, Tse-Ming
中科院分区：
文献类型：
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作者：
Tung, Chia-Hao;Kuo, Li-Wei;Hong, Tse-Ming
卵巢癌(OvCa)的治疗因其高复发率而仍然具有挑战性。癌细胞脱离到腹腔液中在卵巢癌复发中起着关键作用，但这是如何发生的仍不完全清楚。在这里，我们研究了成对的初发/复发性OvCa标本的全局miRNA表达谱，并发现了一个新的生物标记物，microRNA-150-5p(miR-150-5p)，与匹配的原发标本相比，在16例复发性OvCa组织中显著上调。来自另外两组的队列分析证实，miR-150-5p的表达与卵巢癌患者的早期复发和生存不良有关。抑制miR-150-5P可显著抑制OvCa细胞的迁移和侵袭，并诱导间充质-上皮转化(MET)表型。我们证实原癌基因myb是OvCa细胞中的miR-150-5p靶点，miR-150-5p/c-Myb/slug轴在调控OvCa细胞上皮-间充质转化(EMT)中发挥重要作用。MYB的表达与OvCa的良好临床结局显著相关，而与晚期临床标本中的Slug表达呈负相关。这些结果提示miR-150-5p上调通过靶向c-Myb/slug通路介导复发OvCA的进展。抑制miR-150-5p可能成为预防卵巢癌复发的一种新的治疗策略。
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.