NCBP3/SNHG6 inhibits GBX2 transcription in a histone modification manner to facilitate the malignant biological behavior of glioma cells

RNA-binding proteins (RBPs) are significantly dysregulated in glioma. In this study, we demonstrated the upregulation of Nuclear cap binding subunit 3 (NCBP3) in glioma tissues and cells. Further, knockdown of NCBP3 inhibited the malignant progression of glioma. NCBP3 directly bound to small nucleolar RNA host gene 6 (SNHG6) and stabilized SNHG6 expression. In contrast, the gastrulation brain homeobox 2 (GBX2) transcription factor was downregulated in glioma tissues and cells. SNHG6 inhibited GBX2 transcription by mediating the H3K27me3 modification induced by polycomb repressive complex 2 (PRC2). Moreover, GBX2 decreased the promoter activities and downregulated the expression of the flotillin protein family 1 (FLOT1) oncogene. In conclusion, NCBP3/SNHG6 inhibits GBX2 transcription in a PRC2-dependent manner to facilitate the malignant progression of gliomas.

RNA结合蛋白（RNA-binding proteins, RBPs）在胶质瘤中存在显著表达失调。本研究证实，核帽结合亚基3（Nuclear cap binding subunit 3, NCBP3）在胶质瘤组织与细胞中呈高表达。进一步实验表明，敲低NCBP3可抑制胶质瘤的恶性进展。NCBP3可直接结合小核仁RNA宿主基因6（small nucleolar RNA host gene 6, SNHG6）并稳定其表达。与之相反，原肠脑同源框2（gastrulation brain homeobox 2, GBX2）转录因子在胶质瘤组织与细胞中呈低表达。SNHG6可通过介导多梳抑制复合体2（polycomb repressive complex 2, PRC2）诱导的H3K27me3修饰，抑制GBX2的转录。此外，GBX2可降低flotillin蛋白家族1（flotillin protein family 1, FLOT1）癌基因的启动子活性并下调其表达。综上，NCBP3/SNHG6可通过依赖PRC2的方式抑制GBX2转录，从而促进胶质瘤的恶性进展。