Studies have found that RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are dysregulated and play an important regulatory role in the development of tumors. Based on The Cancer Genome Atlas (TCGA) database, our findings from experiments, and the evidence of previous studies, we screened DiGeorge syndrome critical region gene 8 (DGCR8), ZFAT antisense RNA 1 (ZFAT-AS1), and caudal type homeobox 2 (CDX2) as research candidates. In the present study, DGCR8 and CDX2 were highly expressed and ZFAT-AS1 was markedly downregulated in glioma tissues and cells. DGCR8 or CDX2 knockdown or ZFAT-AS1 overexpression suppressed glioma cell proliferation, migration, and invasion and facilitated apoptosis. DGCR8 might decrease ZFAT-AS1 expression by attenuating its stability in a manner of inducing its cleavage. Importantly, ZFAT-AS1 could inhibit CDX2 transcription by mediating the methylation of histone H3 on lysine 27 (H3K27me3) modification induced by PRC2 in the CDX2 promoter region. In addition, CDX2 transcriptionally activated DGCR8 expression by binding to its promoter regions, forming a positive feedback loop of DGCR8/ZFAT-AS1/CDX2. In conclusion, DGCR8/ZFAT-AS1 promotes CDX2 transcription in a PRC2 complex-dependent manner to facilitate the malignant biological behavior of glioma cells.

中文翻译：

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DGCR8 / ZFAT-AS1以依赖PRC2的方式促进CDX2转录，以促进神经胶质瘤细胞的恶性生物学行为。

研究发现，RNA结合蛋白（RBP）和长非编码RNA（lncRNA）失调，在肿瘤的发展中起着重要的调节作用。基于癌症基因组图谱（TCGA）数据库，我们从实验中获得的发现以及先前研究的证据，我们筛选了DiGeorge综合征关键区域基因8（DGCR8），ZFAT反义RNA 1（ZFAT-AS1）和尾状同源框2 （CDX2）作为研究候选人。在本研究中，DGCR8和CDX2在神经胶质瘤组织和细胞中高表达，ZFAT-AS1明显下调。DGCR8或CDX2敲低或ZFAT-AS1过表达抑制神经胶质瘤细胞的增殖，迁移和侵袭，并促进细胞凋亡。DGCR8可能以诱导Z裂解的方式减弱其稳定性而降低ZFAT-AS1的表达。重要的，ZFAT-AS1可以通过介导在CDX2启动子区域中PRC2诱导的赖氨酸27（H3K27me3）修饰上的组蛋白H3甲基化来抑制CDX2转录。另外，CDX2通过结合其启动子区域来转录激活DGCR8表达，从而形成DGCR8 / ZFAT-AS1 / CDX2的正反馈环。总之，DGCR8 / ZFAT-AS1以PRC2复合物依赖性方式促进CDX2转录，以促进神经胶质瘤细胞的恶性生物学行为。