Hand and Foot Surgical Center, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):491-500. doi: 10.1007/s11626-019-00370-3. Epub 2019 Jun 13.
Neurofibromatosis type I (NF1) is a carcinoma mainly featured by malignant peripheral nerve sheath tumor (MPNST). Dysregulated microRNAs (miRNAs) play decisive roles in tumor initiation and development. Our study sought for the possible roles of miR-612 in NF1. RT-qPCR estimated the expression of nuclear factor kappa B subunit 1 (NFKB1), miR-612, and Fas apoptotic inhibitory molecule 2 (FAIM2) in NF1, separately. Cell proliferation and migration were detected by CCK-8 and transwell experiments. Cell apoptosis was measured via flow cytometry and detection of the expression and activity of caspase 3/8/9. Luciferase reporter, ChIP, and RIP assays testified the interplay between studied genes. Rescue and in vivo assays affirmed the whole mechanism of miR-612 in NF1. We indicated that miR-612 was significantly low in tumor tissues and cells. Mechanism experiments confirmed that miR-612 promotion repressed cell proliferation and migration, and induced cell apoptosis. Besides, NFKB1-regulated miR-612 targeted FAIM2. Spearman's correlation analysis validated the correlation between each two genes. Finally, rescue and in vivo assays affirmed that miR-612 targeted FAIM2 to regulate cellular activities of NF1. The current investigation uncovered the molecular mechanism underlying miR-612 in NF1, establishing miR-612 as a novel therapeutic target for the treatment of NF1 patients.
神经纤维瘤病 1 型（NF1）是一种以恶性外周神经鞘瘤（MPNST）为主要特征的癌。失调的 microRNAs（miRNAs）在肿瘤的发生和发展中起着决定性的作用。我们的研究旨在探讨 miR-612 在 NF1 中的可能作用。RT-qPCR 分别评估了 NF1 中核因子 kappa B 亚单位 1（NFKB1）、miR-612 和 Fas 凋亡抑制分子 2（FAIM2）的表达。CCK-8 和 Transwell 实验检测细胞增殖和迁移。通过流式细胞术和 caspase 3/8/9 的表达和活性检测来测量细胞凋亡。荧光素酶报告、ChIP 和 RIP 测定证实了研究基因之间的相互作用。挽救和体内实验证实了 miR-612 在 NF1 中的整体机制。我们表明，miR-612 在肿瘤组织和细胞中明显下调。机制实验证实，miR-612 的促进作用抑制了细胞增殖和迁移，并诱导了细胞凋亡。此外，NFKB1 调节的 miR-612 靶向 FAIM2。Spearman 相关分析验证了每个两个基因之间的相关性。最后，挽救和体内实验证实 miR-612 通过靶向 FAIM2 来调节 NF1 的细胞活性。本研究揭示了 miR-612 在 NF1 中的分子机制，确立了 miR-612 作为治疗 NF1 患者的新型治疗靶点。
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