环状RNA circ-UBXN7通过稳定p53蛋白抑制胶质母细胞瘤恶性生长的分子机制

Circular RNA is a newly discovered non-coding RNA, and its important effect in regulating the malignant growth of glioblastoma (GBM) is still unknown. We have previously demonstrated that non-coding RNAs could play an important role in tumor malignant growth (Leukemia, 2017). Further analysis by RNA-seq in GBM revealed that the expression of circular RNA circ-UBXN7 in GBM was decreased with the increase of malignancy; and interestingly its overexpression significantly inhibited tumor growth, firmly suggesting that circ-UBXN7 could exert important roles in tumor suppression. Moreover, by using protein-circular RNA capture system, circ-UBXN7 was found to bind to p53 protein and enhance p53 protein stability in cells, thus to promote p53 expression. Based on these results, by using RIP, RNA pull down and other experiments combined with high-throughput detection of RNA-seq, we seek to elucidate the inhibitory effect of circ-UBXN7 on the malignant growth of GBM in cells, animal models and clinical samples; to clarify the molecular mechanisms regarding the inhibition of GBM malignant growth by circ-UBXN7 via enhancing p53 protein stability; to explore potential molecular targets that might be potential for the suppression of GBM malignancy, and provide new strategies for more effective GBM treatments.

环状RNA是一种新发现的非编码RNA，其参与调控胶质母细胞瘤（GBM）恶性生长的分子机制不明。我们已证实非编码RNA在肿瘤恶性生长中发挥了重要作用（Leukemia,2017)，进一步对GBM进行RNA-seq检测发现，环状RNA circ-UBXN7在GBM中表达量随恶性程度增加而降低；且它的过表达可显著抑制肿瘤生长，高度提示circ-UBXN7发挥了抑癌作用。进一步利用蛋白-环状RNA捕捉系统发现circ-UBXN7在细胞中可与p53蛋白结合并增强p53蛋白稳定性，促进p53表达。在此基础上，本项目拟采用RIP、RNA垂钓等实验结合RNA-seq等高通量检测手段，在细胞、动物模型及临床样本中，明确circ-UBXN7抑制GBM恶性生长的作用；阐明circ-UBXN7通过增强p53蛋白稳定性抑制GBM恶性生长的分子机制，探寻抑制GBM恶性生长潜在的分子靶标,为更有效治疗GBM提供新策略。

环状RNA是一种新发现的非编码RNA，其参与调控胶质母细胞瘤（GBM）恶性生长的分子机制不明。我们已证实非编码RNA在肿瘤恶性生长中发挥了重要作用（Leukemia,2017)，进一步对GBM进行RNA-seq检测发现，环状RNA circ-UBXN7在GBM中表达量随恶性程度增加而降低；且它的过表达可显著抑制肿瘤生长，高度提示circ-UBXN7发挥了抑癌作用。进一步利用蛋白-环状RNA捕捉系统及发现circ-UBXN7在细胞中可与p53蛋白结合并增强p53蛋白稳定性，促进p53表达。随后本项目在细胞、动物模型及临床样本中，明确circ-UBXN7抑制GBM恶性生长的作用；并且通过RIP、RNA-pulldown等实验结合RNA-seq等高通量检测手段，阐明circ-UBXN7在细胞中通过与p53蛋白结合进而增强p53的蛋白稳定性进而抑制GBM恶性生长的分子机制。我们的研究结果表明circ-UBXN7是抑制GBM恶性生长潜在的分子靶标，为更有效治疗GBM提供了新策略。