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.
PLoS One. 2018 Mar 13;13(3):e0193709. doi: 10.1371/journal.pone.0193709. eCollection 2018.
Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs).
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.
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.
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.
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。
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。
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。
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。
