Department of Urology, QiLu Hospital of Shandong University, Jinan 250012, Shandong, P.R. China.
Department of Gynecology, Jinan Central Hospital, Jinan 250012, Shandong, P.R. China.
Aging (Albany NY). 2020 May 19;12(10):8880-8892. doi: 10.18632/aging.103007.
lncRNA can interact with miRNA as a ceRNA to participate in the regulation of target gene expression, thus playing an important role in the development of malignant tumors. In this research, we found that OGFRP1 was up-regulated in prostate cancer (PCa) clinical samples and cell lines. Additionally, OGFRP1 is significantly associated with TNM stages III and IV and perineural invasion. Knockdown of OGFRP1 inhibited the growth of PCa cells, suggesting a promotional effect of OGFRP1 in tumor progression. Interestingly, OGFRP1 primarily localized in the cytoplasm, while miR-124-3p was found to bind to OGFRP1. Therefore, we further analyzed the downstream target of miR-124-3p using TargetScan. The result of the luciferase reporter gene assay displayed that SARM1 was a downstream target of miR-124-3p in two PCa cell lines. The overexpression of SARM1 promoted growth and metastasis in PCa cells. Knockdown of OGFRP1 and overexpression of miR-124-3p markedly restored the promotion of SARM1 to PCa cells. In conclusion, lncRNA OGFRP1 completely bound to miR-124-3p and relieved their inhibition on SARM1, thus promoting the growth of PCa cells. This report extended our understanding of the underlying molecular mechanisms of lncRNAs in PCa, which could help us find novel diagnostic and therapeutic targets.
lncRNA 可以作为 ceRNA 与 miRNA 相互作用,参与靶基因表达的调控,从而在恶性肿瘤的发生发展中发挥重要作用。在本研究中,我们发现 OGFRP1 在前列腺癌(PCa)临床样本和细胞系中上调。此外,OGFRP1 与 TNM 分期 III 和 IV 以及神经周围浸润显著相关。OGFRP1 的敲低抑制了 PCa 细胞的生长,表明 OGFRP1 在肿瘤进展中具有促进作用。有趣的是,OGFRP1 主要定位于细胞质,而 miR-124-3p 被发现与 OGFRP1 结合。因此,我们使用 TargetScan 进一步分析了 miR-124-3p 的下游靶标。荧光素酶报告基因检测结果显示,在两种 PCa 细胞系中,SARM1 是 miR-124-3p 的下游靶标。SARM1 的过表达促进了 PCa 细胞的生长和转移。OGFRP1 的敲低和 miR-124-3p 的过表达显著恢复了 SARM1 对 PCa 细胞的促进作用。总之,lncRNA OGFRP1 完全与 miR-124-3p 结合,解除了它们对 SARM1 的抑制作用,从而促进了 PCa 细胞的生长。该报告扩展了我们对 lncRNA 在 PCa 中潜在分子机制的理解,这有助于我们发现新的诊断和治疗靶点。