miR-99a-5p在MDS患者骨髓中的表达及功能分析

Expression and Function of miR-99a-5p in Bone Marrow of Patients with MDS

目的:检测miR-99a-5p在骨髓增生异常综合症(MDS)患者中的表达,利用生物信息学预测其靶基因并进行功能分析,探讨miR-99a-5p在MDS的发生发展中可能的作用。方法:利用qRT-PCR技术检测miR-99a-5p在初治MDS患者骨髓中的表达量,分析其与MDS临床病理参数的相关性;运用靶基因在线预测软件Targetscan、Miranda和Microcosm预测其可能的靶基因,取预测结果的交集作为miR-99a-5p在MDS中的潜在靶基因。结果:与正常对照组相比,MDS患者骨髓中miR-99a-5p表达升高(P<0.001)。按IPSS的预后评分,将MDS患者分为相对低危组(包括低危险组和中危1组)和相对高危组(包括中危2组和高危组)发现,在相对低危组中miR-99a-5p的表达量是正常对照组的2.40倍(P<0.001),相对高危组中miR-99a-5p的表达量是对照组的6.66倍(P<0.001),相对高危组中miR-99a-5p表达量是相对低危组的2.80倍(P<0.001);转白血病组(t-MDS)中miR-99a-5p的表达量是对照组的6.35倍(P<0.001)。相关分析显示,患者骨髓miR-99a-5p表达量与原始细胞比例呈显著正相关(P<0.001);而与染色体核型、外周血血象无明显相关。利用靶基因在线预测软件预测mi R-99a-5p的可能靶基因,并结合文献,得出ST5可能是mi R-99a-5p在MDS中的潜在靶基因。结论:mi R-99a-5p在MDS患者中表达明显上调,且随着危险度的增加其表达呈上升趋势,并可能通过负性调控靶基因ST5参与MDS的发病。

Objective: To detect the expression of miR-99a-5p in myelodysplastic syndrome(MDS), to predict the target genes and to analyze its function by using bioinformatics. Methods: The expression levels of bone marrow miR-99a-5p in MDS patients were detected by qRT-PCR, and the correlation of miR-99a-5p expression with clinical pathological characteristics, percentage of marrow blasts, chromosome karyotype and peripheral blood hemogram were analyzed. The target genes of miR-99a-5p were predicted by Targetscan, Miranda and Microcosm, and the intersection of the predicted results of 3 softwares was used as a potential target gene for miR-99a-5p. Results: The expression level of bone marrow miR-99a-5p in MDS patients was significantly higher than that of healthy controls(P<0.01);According to the prognostic score of IPSS, MDS patients were divided into relatively low risk group(including low risk group and intermediate risk group 1) and relatively high risk group(including intermediate risk group 2 and high risk group). Analysis showed that the expression level of bone marrow miR-99a-5p in relatively low risk group was 2.40 times higher than that in healthy control group(P <0.01), the expression level of bone marrow miR-99a-5p in relatively high risk group was 6.66 times higher than that in healthy control group(P <0.01), the expression level of miR-99a-5p in relatively high risk group was 2.80 times higher than that in the relatively low risk group( P <0.01);the expression level of bone marrow miR-99a-5p in t-MDS group was 6.35 times higher than that in healthy control group(P <0.001). There was a significant positive correlation between the expression level of miR-99a-5p and the percentage of marrow blasts(P <0.01), but the expression of miR-99a-5p did not correlate with chromosome karyotype and peripheral blood hemogram;In this study it was obtained that ST5 might participate in pathological mechanism of MDS by bioinformatic analyses and references. Conclusion: The expression levels of miR-99a-5p is up-regulated in MDS patients, and its expression showed a rising tendency which may be involved in the pathogenesis of MDS by regulating target gene ST5.