循环 CD133 阳性细胞 miRNA 特征在 HCV 感染的肝细胞癌中的研究。
MicroRNA Signatures for circulating CD133-positive cells in hepatocellular carcinoma with HCV infection.
机构信息
Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
出版信息
PLoS One. 2018 Mar 13;13(3):e0193709. doi: 10.1371/journal.pone.0193709. eCollection 2018.
AIM
Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs).
METHODS
We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array.
RESULTS
The differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and miR-192 were significantly up regulated (fold change = 13, 3.1, 2.8, 1.6 & 1.56, P value = 0.01, 0.001, 0.000004, 0.002 & 0.007 respectively). Upon comparing the HCC group to the LC group; miR-199a-3p, miR-192, miR-122, miR-181b, miR-224, miR-125a-5p, and miR-885-5p were significantly up regulated (fold change = 5, 6.7, 2.3, 3, 2.5, 4.2 & 39.5 P value = 0.001025, 0.000024, 0.000472, 0.000278, 0.000004, 0.000075 & 0.0000001 respectively) whereas miR-22 was significantly down regulated (fold change = 0.57 P value = 0.00002). Only, miR-192, miR-122, miR-181b and miR-125a-5p were significant common miRNAs in CD133+ cells of the HCC group compared to the other non-malignant groups.
CONCLUSION
We identified a miRNA panel comprised of four miRNAs (miR-192, miR-122, miR-181b and miR-125a-5p) that may serve as a molecular tool for characterization of the CD133+ cells associated with different stages of hepatocarinogensis. This panel may aid in developing a new target therapy specific for those CD133+ cells.
目的
通过鉴定特定 microRNAs（miRNAs）的表达模式，对与肝发生相关的 CD133+干细胞进行分子特征分析。
方法
我们使用定制的 miScript miRNA PCR 阵列，研究了从健康志愿者、慢性丙型肝炎（CHC）、肝硬化（LC）和肝细胞癌（HCC）患者外周血中分离的 CD133+细胞中 13 种 miRNA 的表达模式，以及来自健康志愿者和 LC 患者的骨髓样本。
结果
与对照组相比，来自 HCC 患者外周血的 CD133+细胞中 13 种研究 miRNA 的差异表达显示，miR-602、miR-181b、miR-101、miR-122、miR-192、miR-125a-5p 和 miR-221 明显上调（倍数变化=1.8、1.7、2、5.4、1.6、2.9 和 1.5，P 值=0.039、0.0019、0.0013、0.0370、0.0024、0.000044 和 0.000007）。与 CHC 组相比，HCC 组的 miR-602、miR-122、miR-181b、miR-125a-5p 和 miR-192 明显上调（倍数变化=13、3.1、2.8、1.6 和 1.56，P 值=0.01、0.001、0.000004、0.002 和 0.007）。与 LC 组相比，HCC 组的 miR-199a-3p、miR-192、miR-122、miR-181b、miR-224、miR-125a-5p 和 miR-885-5p 明显上调（倍数变化=5、6.7、2.3、3、2.5、4.2 和 39.5，P 值=0.001025、0.000024、0.000472、0.000278、0.000004、0.000075 和 0.0000001），而 miR-22 明显下调（倍数变化=0.57，P 值=0.00002）。与其他非恶性组相比，只有 miR-192、miR-122、miR-181b 和 miR-125a-5p 是 HCC 组 CD133+细胞中共同存在的显著 miRNA。
结论
我们鉴定了一个由四个 miRNA（miR-192、miR-122、miR-181b 和 miR-125a-5p）组成的 miRNA 谱，该谱可能作为鉴定与肝发生不同阶段相关的 CD133+细胞的分子工具。该谱可能有助于开发针对这些 CD133+细胞的新靶向治疗方法。
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