Li Wei, Zhong Chaoqin, Jiao Jun, Li Peng, Cui Baoxia, Ji Chunyan, Ma Daoxin
Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China.
Int J Mol Sci. 2017 Mar 9;18(3):597. doi: 10.3390/ijms18030597.
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.
环状RNA（circRNAs）是一类广泛存在的非编码RNA，过去鲜受关注。最近，有限的数据显示它们在人类癌症中作为生物标志物有着广阔前景，但在血液系统恶性肿瘤，尤其是白血病中，其特征和功能仍大多未知。在本研究中，借助circRNA微阵列，我们展示了急性髓系白血病（AML）患者中circRNAs的表达谱，并鉴定出大量可能以白血病特异性方式表达的circRNAs。我们还基于生物信息学预测描述了一种与AML风险状态相关的circRNA特征。特别地，对一个包含115个人类样本的队列中的一个下调的circRNA，即hsa_circ_0004277进行了表征和功能评估，从而为AML提供了一个潜在的诊断标志物和治疗靶点。有趣的是，我们发现化疗可显著恢复hsa_circ_0004277的表达，表明hsa_circ_0004277水平的升高与治疗成功相关。此外，还展示了hsa_circ_0004277详细的circRNA- miRNA- mRNA相互作用网络，使我们能够更好地理解其在AML中发挥功能的潜在机制。
