[Expression Level and Target Gene Prediction of miR-181b in Patients with Chronic Lymphocytic Leukemia]

To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics.Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes.The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging.The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.miR-181b在慢性淋巴细胞白血病患者中的表达及其靶基因的预测.探讨miR-181b在慢性淋巴细胞白血病（CLL）患者CD19+B淋巴细胞中的表达水平，分析其表达与CLL预后关系，并利用生物信息学预测miR-181b在CLL中的潜在靶基因.选取2013年6月至2018年6月在新疆自治区人民医院诊治的CLL患者84例、并选取健康者20例为对照组。应用磁珠分选CLL患者和对照组外周血CD19+ B淋巴细胞后进行RNA提取，检测miR-181b的表达水平，分析其在不同IPI分组中表达差异，探讨miR-181b表达水平与CLL患者PFS相关性。使用网上数据库及文献预测miR-181b靶基因,对候选靶基因进行基因注释分析及相关信号通路分析.miR-181b在CLL患者中表达显著低于对照组（P＜0.01）。miR-181b在低危组的表达水平高于高危组和极高危组（P＜0.05），但在低危组与中危组间表达无差异（P=1.00），中危组中miR-181b的表达水平高于高危组和极高危组（P＜0.05）,但在高危组与极高危组间表达无差异。ROC曲线结果显示，曲线下面积（AUC）为0.792（P＜0.01）， 由此显示，miR-181b表达水平处于分界值0.279时，具有较好的敏感性（62.9%）和特异性（91.8%）。生存分析结果提示，与高表达组相比，miR-181b低表达CLL患者具有较差的PFS（log-rank：P=0.047）。使用starBase、Targetscan和PicTar数据库进行靶基因预测，结合文献报道，与血液疾病相关的靶基因有CARD11、ZFP36L1、RUNX1、NR4A3、ATP1B1、PUM1和PLAG1，其中上调的CARD11、ZFP36L1通过促进细胞增殖、抑制细胞衰老参与淋巴系统肿瘤形成.miR-181b在CLL患者中的表达水平明显低于健康对照组，且miR-181b低表达与CLL不良预后有关。通过生物信息学预测并结合文献报道，推测CARD11及ZFP36L1可能作为miR-181b的靶基因参与CLL疾病发生发展，该结果还需要进一步实验进行验证.