Next Generation Sequencing Analysis of miRNAs: MiR-127-3p Inhibits Glioblastoma Proliferation and Activates TGF-β Signaling by Targeting SKI
Next Generation Sequencing Analysis of miRNAs: MiR-127-3p Inhibits Glioblastoma Proliferation and Activates TGF-β Signaling by Targeting SKI
复制标题
DOI：
10.1089/omi.2013.0122
复制
发表时间：
2014-03-01
影响因子：
3.3
通讯作者：
Lin, Biaoyang
中科院分区：
文献类型：
--
作者：
Jiang, Huawei;Jin, Chengmeng;Lin, Biaoyang
胶质母细胞瘤（GBM）增殖是一个多步骤的过程，在此过程中，控制细胞增殖，细胞死亡和遗传稳定性的许多基因的表达水平发生改变。微小RNA（miRNAs）正在成为细胞信号传导的重要调节剂，包括癌症中的细胞增殖。在这项研究中，使用新一代的miRNA测序分析，我们发现，与正常脑组织相比，miR-127- 3 p在GBM组织中下调;我们通过RT-PCR验证了这一结果。我们进一步表明，DNA去甲基化和组蛋白去乙酰化酶抑制导致miR-127- 3 p下调。我们证明miR-127- 3 p过表达通过诱导G1期阻滞抑制GBM细胞生长。我们发现miR-127- 3 p靶向SKI（v-ski肉瘤病毒癌基因同源物[禽类]）、RGMA（RGM结构域家族，成员A）、ZWINT（ZW 10相互作用物，动粒蛋白）、SERPINB 9（丝氨酸蛋白酶抑制剂，进化枝B [卵白蛋白]，成员9）和SFRP 1（分泌型卷曲相关蛋白1）。最后，我们发现miR-127- 3 p通过抑制促肿瘤SKI和激活转化生长因子-β（TGF-β）信号传导的肿瘤抑制作用来抑制GBM细胞生长。这项研究首次表明，miR-127- 3 p及其靶基因SKI在GBM中发挥重要作用，并可能成为GBM治疗的潜在靶点。
Glioblastoma (GBM) proliferation is a multistep process during which the expression levels of many genes that control cell proliferation, cell death, and genetic stability are altered. MicroRNAs (miRNAs) are emerging as important modulators of cellular signaling, including cell proliferation in cancer. In this study, using next generation sequencing analysis of miRNAs, we found that miR-127-3p was downregulated in GBM tissues compared with normal brain tissues; we validated this result by RT-PCR. We further showed that DNA demethylation and histone deacetylase inhibition resulted in downregulation of miR-127-3p. We demonstrated that miR-127-3p overexpression inhibited GBM cell growth by inducing G1-phase arrest both in vitro and in vivo. We showed that miR-127-3p targeted SKI (v-ski sarcoma viral oncogene homolog [avian]), RGMA (RGM domain family, member A), ZWINT (ZW10 interactor, kinetochore protein), SERPINB9 (serpin peptidase inhibitor, clade B [ovalbumin], member 9), and SFRP1 (secreted frizzled-related protein 1). Finally, we found that miR-127-3p suppressed GBM cell growth by inhibiting tumor-promoting SKI and activating the tumor suppression effect of transforming growth factor-beta (TGF-beta) signaling. This study showed, for the first time, that miR-127-3p and its targeted gene SKI, play important roles in GBM and may serve as potential targets for GBM therapy.