Despite progress in conventional treatment for glioblastoma (GBM), the prognosis remains poor due to high tumor recurrence. Therefore, identification of new molecular mechanisms is a pressing need for betterment of GBM patient outcomes. qRT-PCR was used to determine BDNF-AS expression in GBM cells. CCK-8, EdU incorporation, and caspase-3 activity assays were employed to analyze biological functions of BDNF-AS. RIP and RNA pull-down were conducted to detect the interactions among BDNF-AS, ADAR, and p53. Actinomycin D was utilized to examine the stability of p53 mRNA. ChIP and luciferase reporter assays were performed to detect transcriptional activation of BDNF-AS by p53. We found that BDNF-AS was significantly downregulated in GBM cell lines, and its overexpression inhibited GBM cell growth, and promoted apoptosis. Importantly, we illustrated that BDNF-AS coupled with ADAR protein to potentiate stability of p53 mRNA and thus upregulate p53. Interestingly, we further identified p53 as a transcription factor of BDNF-AS, activating transcription of BNDF-AS. This study firstly demonstrated that BDNF-AS acted as a tumor suppressor in GBM and the positive feedback circuit of BDNF-AS/ADAR/p53 served an important mechanism to control GBM proliferation. Targeting this auto-regulatory loop may provide a potential therapeutic strategy for GBM patients.

中文翻译：

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BDNF-AS / ADAR / p53正反馈环的激活抑制胶质母细胞瘤细胞增殖。

尽管胶质母细胞瘤（GBM）的常规治疗取得了进展，但由于肿瘤的高复发率，预后仍然很差。因此，鉴定新的分子机制是改善GBM患者预后的迫切需要。qRT-PCR用于确定GBM细胞中的BDNF-AS表达。使用CCK-8，EdU掺入和caspase-3活性测定来分析BDNF-AS的生物学功能。进行了RIP和RNA下拉检测，以检测BDNF-AS，ADAR和p53之间的相互作用。放线菌素D用于检查p53 mRNA的稳定性。进行了ChIP和荧光素酶报告基因检测，以检测p53对BDNF-AS的转录激活。我们发现，BDNF-AS在GBM细胞系中显着下调，其过表达抑制GBM细胞的生长，并促进细胞凋亡。重要的，我们举例说明了BDNF-AS与ADAR蛋白偶联增强了p53 mRNA的稳定性，从而上调了p53。有趣的是，我们进一步将p53鉴定为BDNF-AS的转录因子，激活BNDF-AS的转录。这项研究首先证明了BDNF-AS在GBM中起着抑癌作用，而BDNF-AS / ADAR / p53的正反馈电路是控制GBM增殖的重要机制。靶向这种自动调节回路可能为GBM患者提供潜在的治疗策略。这项研究首先证明了BDNF-AS在GBM中起着抑癌作用，而BDNF-AS / ADAR / p53的正反馈电路是控制GBM增殖的重要机制。靶向这种自动调节回路可能为GBM患者提供潜在的治疗策略。这项研究首先证明了BDNF-AS在GBM中起着抑癌作用，而BDNF-AS / ADAR / p53的正反馈电路是控制GBM增殖的重要机制。靶向这种自动调节回路可能为GBM患者提供潜在的治疗策略。