IL-1β 诱导的 NF-κB 激活下调 miR-506 的表达，通过 JAG1 促进骨肉瘤细胞生长。
IL-1β-induced NF-κB activation down-regulates miR-506 expression to promotes osteosarcoma cell growth through JAG1.
机构信息
Department of Anatomy, Histology and Embryology, Changsha Medical University, Changsha 410219,China.
Changsha Medical University, Changsha, 410219,China.
出版信息
Biomed Pharmacother. 2017 Nov;95:1147-1155. doi: 10.1016/j.biopha.2017.08.120. Epub 2017 Oct 6.
Nowadays, the role of miRNA in tumorigenesis has been largely reported. It was found that miR-506 might be associated with tumorigenesis of various cancers. The present study was aimed to investigate the character of miR-506 and some related factors in human osteosarcoma (OS) carcinogenesis. The expression level of miR-506 was downregulated in OS compared with the normal control group by RT-PCR, both in vivo and in vitro. In addition, IL-1β stimulation decreased the expression of miR-506. MiR-506 interfered with JAG1 gene transcription throughmiR-506 binding to the 3'-UTR region of JAG1 gene. Further siRNA strategy suggested that IL-1β may regulate miR-506 level via NF-κB, and then alter the JAG1 expression. Besides, the suppression of JAG1 by miR-506 inhibited OS cell proliferation. Taken together, our data indicate a process of NF-κB-induced miR-506 suppression and JAG1 upregulation upon IL-1β induction, which can be regarded as a new pathway for modulating cell proliferation via miR-506. It may be of clinical value in treating OS in the future.
如今，miRNA 在肿瘤发生中的作用已被大量报道。研究发现，miR-506 可能与多种癌症的肿瘤发生有关。本研究旨在探讨 miR-506 及其在人类骨肉瘤（OS）发生中的一些相关因素的特征。通过 RT-PCR，无论是在体内还是体外，OS 中的 miR-506 表达水平均低于正常对照组。此外，IL-1β 刺激可降低 miR-506 的表达。miR-506 通过与 JAG1 基因 3'-UTR 区域结合干扰 JAG1 基因的转录。进一步的 siRNA 策略表明，IL-1β 可能通过 NF-κB 调节 miR-506 水平，从而改变 JAG1 的表达。此外，miR-506 对 JAG1 的抑制作用抑制了 OS 细胞的增殖。总之，我们的数据表明，在 IL-1β 诱导下，NF-κB 诱导的 miR-506 抑制和 JAG1 上调是一个新的途径，可以通过 miR-506 调节细胞增殖。这在未来治疗骨肉瘤方面可能具有临床价值。
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