SET7/9 在长链非编码 RNA DRAIC 启动子上促进 H3K4me3 以调节神经胶质瘤的生长和转移。
SET7/9 promotes H3K4me3 at lncRNA DRAIC promoter to modulate growth and metastasis of glioma.
机构信息
Department of Neurosurgery, Chinese PLA General Hospital, Beijing City, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12241-12250. doi: 10.26355/eurrev_202012_24016.
OBJECTIVE
We aimed at investigating the expression levels of SET7/9 in glioma and the relationship between SET7/9 and LncRNA DRAIC. Further, we explored the relationship between SET7/9 and glioma cell metastasis and mood.
PATIENTS AND METHODS
The expression levels of DRAIC and miR-18a-3p in gastric cancer cells were measured by quantitative polymerase chain reaction (qPCR). The binding site of the promoter of DRAIC by H3K4me3 was confirmed by ChIP-Real-time PCR. The direct target of DRAIC and miR-18a-3p in gastric cancer cells was measured by a Luciferase reporter assay. Cell proliferation was detected by Cell counting kit-8 (CCK8), and cell invasion and migration were measured by transwell assays.
RESULTS
Compared with adjacent non-cancerous normal tissues, SET7/9 and DRAIC were both downregulated and miR-18a-3p was upregulated in glioma cells. Meanwhile, silencing of SET7/9 enhanced cell proliferation, migration, and invasion in U251 cells. H3K4me3 protein can bind to DRAIC promoter directly. Inhibition of SET7/9 and downregulation of DRAIC in U251 cells reversed the effect of SET7/9 silencing on the growth and metastasis of glioma cells. In U251 cells, SET7/9 and DRAIC overexpression inhibited cell proliferation, migration and invasion. In addition, miR-18a-3p interacts with DRAIC through direct binding. The inhibition of DRAIC promoted the growth and metastasis of U251 cells, while the co-transfection of si- DRAIC and miR-18a-3p further promoted the growth and metastasis of U251 cells. Overexpression of DRAIC inhibited the growth and metastasis of cells, completely reversing the co-transfection of Lnc-DRAIC and miR-18a-3p.
CONCLUSIONS
In this research, we discovered that the expression of SET7/9 was low in glioma cells and SET7/9-mediated H3K4me3 enrichment on the DRAIC promoter regulated the growth and metastasis of glioma cells by targeting miR-18a-3p. It potentially provides a new therapeutic marker targeting glioma.
目的
我们旨在研究 SET7/9 在神经胶质瘤中的表达水平，以及 SET7/9 与长链非编码 RNA DRAIC 之间的关系。此外，我们还探讨了 SET7/9 与神经胶质瘤细胞转移和情绪之间的关系。
患者和方法
通过实时定量聚合酶链反应（qPCR）测量胃癌细胞中 DRAIC 和 miR-18a-3p 的表达水平。通过 ChIP-Real-time PCR 证实 DRAIC 启动子上 H3K4me3 的结合位点。通过荧光素酶报告基因测定测量胃癌细胞中 DRAIC 和 miR-18a-3p 的直接靶标。通过细胞计数试剂盒-8（CCK8）检测细胞增殖，通过 Transwell 测定测量细胞侵袭和迁移。
结果
与相邻的非癌性正常组织相比，SET7/9 和 DRAIC 在神经胶质瘤细胞中均下调，而 miR-18a-3p 上调。同时，沉默 SET7/9 增强了 U251 细胞的增殖、迁移和侵袭。H3K4me3 蛋白可直接结合 DRAIC 启动子。在 U251 细胞中，抑制 SET7/9 和下调 DRAIC 逆转了 SET7/9 沉默对神经胶质瘤细胞生长和转移的影响。在 U251 细胞中，SET7/9 和 DRAIC 的过表达抑制细胞增殖、迁移和侵袭。此外，miR-18a-3p 通过直接结合与 DRAIC 相互作用。抑制 DRAIC 促进了 U251 细胞的生长和转移，而共转染 si-DRAIC 和 miR-18a-3p 进一步促进了 U251 细胞的生长和转移。DRAIC 的过表达抑制了细胞的生长和转移，完全逆转了 Lnc-DRAIC 和 miR-18a-3p 的共转染。
结论
在这项研究中，我们发现 SET7/9 在神经胶质瘤细胞中的表达较低，SET7/9 介导的 DRAIC 启动子上的 H3K4me3 富集通过靶向 miR-18a-3p 调节神经胶质瘤细胞的生长和转移。它可能为神经胶质瘤的治疗提供了一个新的靶点。
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