Reduction of circular RNA expression associated with human retinoblastoma
Reduction of circular RNA expression associated with human retinoblastoma
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与人视网膜母细胞瘤相关的环状 RNA 表达减少
DOI：
10.1016/j.exer.2019.03.017
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Zhao, Peiquan
中科院分区：
文献类型：
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作者：
Lyu, Jiao;Wang, Yu;Zhao, Peiquan
本研究探讨了与人视网膜母细胞瘤（RB）相关的环状RNA（circRNA）表达谱及其表观遗传作用。收集来自未治疗的RB患者的12个配对的原发性样品（原发性RB样品和相应的相邻正常视网膜样品）和来自治疗后复发的RB患者的8个复发性RB样品。在四个配对的原始样品中进行核糖体-RNA耗尽测序。进行定量聚合酶链反应以验证其他八对初级样本和八个复发性RB样本中的circRNA和mRNA表达。应用生物信息学分析预测肿瘤信号通路和circRNA的结合microRNA（miRNA）。结果，通过RNA测序鉴定了总共47640个circRNA，相对于匹配的正常视网膜样品，原发性RB样品中circRNA的丰度较低[22366（47%）对37161（78%），P < 0.001]。在RB和正常视网膜样本中的11887个重叠circRNA中，与正常视网膜样本相比，原发性RB样本中有550个circRNA下调，7个上调。差异表达的circRNA的宿主基因与染色质修饰相关。TET 1-has_circ_0093996（ten-eleven translocation-1），其宿主基因TET 1参与染色质修饰，在原发性和复发性RB样品中均下调。程序性细胞死亡4（PDCD 4）在原发性和复发性RB样品中也下调。我们使用生物信息学工具构建了一个完整的调控轴，包括调节RB发病机制的TET 1-has_circ_0093996-miR-183-PDCD 4。总之，circRNA表达在RB肿瘤中下调，这表明circRNA对RB发病机制的表观遗传调节。
This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). Twelve paired primary samples from un-treated RB patients (primary RB samples and corresponding adjacent normal retinal samples) and eight recurrent RB samples from RB patients having recurrence after treatment were collected. Ribosomal-RNA depleted sequencing was performed in four paired primary samples. Quantitative polymerase chain reaction was conducted to validate circRNA and mRNA expression in the other eight paired primary samples and in eight recurrent RB samples. Bioinformatic analysis was applied to predict the oncological signal pathways and the binding microRNA (miRNA) of circRNA. As a result, a total of 47640 circRNAs were identified by RNA-sequencing, with a lower abundance of circRNAs in primary RB samples relative to matched normal retinal samples [22366 (47%) versus 37161 (78%), P < 0.001]. Among the 11887 overlapping circRNAs in both RB and normal retinal samples, 550 circRNAs were downregulated and seven were upregulated in primary RB samples compared to normal retinal samples. The host genes of the differentially expressed circRNAs were associated with chromatin modification. TET1-has_circ_0093996 (ten-eleven translocation-1), whose host gene TET1 participates in chromatin modifying, was downregulated in both primary and recurrent RB samples. Programmed cell death 4 ( PDCD4) was also downregulated in both primary and recurrent RB samples. We used bioinformatic tools to construct a complete regulatory axis including TET1-has_circ_0093996-miR-183-PDCD4 that regulates RB pathogenesis. In conclusion, circRNA expression is downregulated in RB tumor, which suggests epigenetic regulation of RB pathogenesis by circRNAs.