Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia via Circular RNA Profile and Bioinformatics Analysis.

Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia via Circular RNA Profile and Bioinformatics Analysis.
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通过环状 RNA 谱和生物信息学分析表征 hsa_circ_0004277 作为急性髓系白血病的新生物标志物。

DOI:
10.3390/ijms18030597
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发表时间:
2017-03-09
影响因子:
5.6
通讯作者:
Ma D
Ma D
中科院分区:
生物学2区
文献类型:
--
作者:
Li W;Zhong C;Jiao J;Li P;Cui B;Ji C;Ma D

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环状RNA(CircRNAs)是一类广泛存在的非编码RNA,过去很少引起人们的注意。最近,有限的数据显示了它们作为人类癌症生物标志物的前景,但在血液系统恶性肿瘤中,特别是在白血病中,它们的特征和功能仍然很不清楚。在本研究中,我们借助CircRNA微阵列,展示了CircRNAs在急性髓系白血病(AML)患者中的表达谱,并鉴定了大量可能以白血病特异性方式表达的CircRNA。我们还描述了基于生物信息学预测的与AML风险状态相关的CircRNA特征。特别是,下调的CircRNA hsa_CIRC_0004277在115例人类样本中被鉴定和功能评估,从而提供了一个潜在的急性髓细胞白血病的诊断标记和治疗靶点。有趣的是,我们发现化疗可以显著恢复hSA_CIRC_0004277的表达,提示hSA_CIRC_0004277水平的升高与治疗的成功有关。此外,我们还为hsa_circ_0004277提供了一个详细的CircRNA-miRNA-mR-NA相互作用网络,使我们能够更好地了解其在急性髓系白血病中的作用机制。
Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs, which drew little attention in the past. Recently, limited data showed their promising future to act as biomarkers in human cancer, but the characteristics and functions remain largely unknown in hematopoietic malignancies, especially in leukemia. In this study, with the help of circRNA microarray, we demonstrated the expression profile of circRNAs in acute myeloid leukemia (AML) patients, and identified a large number of circRNAs possibly expressed in a leukemia specific manner. We also described a circRNA signature related to AML risk-status based on the bioinformatics prediction. In particular, a downregulated circRNA, hsa_circ_0004277, was characterized and functionally evaluated in a cohort of 115 human samples, thus offering a potential diagnostic marker and treatment target in AML. Interestingly, we found chemotherapy could significantly restore the expression of hsa_circ_0004277, indicating the increasing level of hsa_circ_0004277 was associated with successful treatment. Furthermore, a detailed circRNA–miRNA–mRNA interaction network was presented for hsa_circ_0004277, allowing us to better understand its underlying mechanisms for function in AML.