The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa. Functional studies were performed in a series of PCa cell lines. In LNCaP cells, miR-410 overexpression led to decreases in cellular viability, proliferation, invasiveness, and migration. On the other hand, miR-410 overexpression in PC3 and C42B cells led to increased viability, proliferation, and invasiveness. Our data suggest that miR-410 represses epithelial-to-mesenchymal transition (EMT) in LNCaP cells by directly repressing SNAIL. However, it promotes EMT and upregulates PI3K/Akt signaling in PC3 and C42B cells. In vivo studies with PC3 xenografts support an oncogenic role of miR-410. These data suggest that miR-410 acts as a tumor suppressor in the initial stages of PCa and play an oncogenic role in advanced PCa. Our findings have important implications in understanding the molecular basis of PCa progression with potential translational implications.
前列腺癌从前列腺癌进展为转移性去势抵抗性前列腺癌，进而发展为治疗诱导的神经内分泌前列腺癌的分子基础尚未完全阐明。本研究旨在阐明位于DLK1-DIO3基因簇14q32.31染色体区域、研究较少的微小RNA miR-410在前列腺癌中的作用。通过对原发性和转移性前列腺癌组织及细胞系中miR-410表达水平的分析，发现其在疾病初期表达降低，而在晚期表达升高。在一系列前列腺癌细胞系中进行的功能研究表明：在LNCaP细胞中，过表达miR-410可降低细胞活力、增殖能力、侵袭性和迁移能力；而在PC3和C42B细胞中，miR-410过表达则促进细胞活力、增殖和侵袭能力。实验数据表明，miR-410通过直接抑制SNAIL来抑制LNCaP细胞的上皮-间质转化过程，但在PC3和C42B细胞中却促进上皮-间质转化并上调PI3K/Akt信号通路。PC3异种移植模型的体内实验进一步支持miR-410的促癌作用。这些数据表明，miR-410在前列腺癌初期发挥抑癌作用，而在晚期则具有促癌功能。本研究对理解前列腺癌进展的分子机制具有重要意义，并具有潜在的转化应用价值。
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