SET7/9 promotes H3K4me3 at lncRNA DRAIC promoter to modulate growth and metastasis of glioma

C. Li, S.-Y. Feng, L. Chen

Department of Neurosurgery, Chinese PLA General Hospital, Beijing City, China. badlc301@126.com

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• Oncology

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.

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