miRNA和Th17相关细胞因子在多发性骨髓瘤患者中的表达及其意义

Potential relationship and clinical significance of miRNAs and Th17 related cytokines in patients with multiple myeloma

目的 探讨miRNA和Th17相关细胞因子在多发性骨髓瘤（MM）患者发病中的作用机制.方法 收集27例MM患者骨髓标本,以8名健康人为正常对照,应用荧光实时定量PCR（qRT-PCR）法检测其miR-15a/16、-34a、-194-2-192簇、-181a/b的表达情况,采用ELISA法检测患者血清Th17相关细胞因子IL-17、IL-21、IL-22、IL-23、IL-27的表达水平.分析miRNA与Th17相关细胞因子表达的相关性.结果 与对照组比较,MM患者组miR-15a/16、-34a、-194-2-192簇表达水平降低,而miR-181a/b表达水平升高,差异均有统计学意义（P值均＜0.05）;MM患者血清IL-17、IL-21、IL-27的表达水平升高,IL-22表达水平降低,差异均有统计学意义（P值均＜0.05）;IL-23表达水平与对照组相比差异无统计学意义（P＞0.05）.ISS分期Ⅲ期患者的miR-181a/b和IL-17、IL-21、IL-23、IL-27表达水平高于Ⅰ期患者,而miR-15a/16、-34a、-194和IL-22的表达水平则低于后者,差异均有统计学意义（P值均＜0.05）.miR-34a与IL-21,miR-181a与IL-23,miR-192与IL-21、IL-27,miR-194与IL-27的表达水平均呈正相关,而miR-192与IL-21呈负相关（P值均＜0.05）.结论 miRNA和Th17相关细胞因子在MM患者中均存在异常表达,其表达水平与MM患者的ISS分期有关,同时两者之间也存在密切的联系,提示失调的miRNA可能影响Th17细胞的分化进而参与MM的发生、发展.

Objective To explore the expression and significance of miRNAs and Th17 related cytokines in patients with multiple myeloma （MM）.Methods A total of 27 MM patients and 8 health controls were enrolled in this study.The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster and miR-181a/b in bone marrow were detected by real-time quantitative PCR （qRT-PCR）.Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of Th17 related cytokines interleukin-17 （IL-17）,IL-21,IL-22,IL-23 and IL-27 in peripheral blood plasma.The role of miRNAs and Th17 related cytokines was analyzed in the development of MM.Results The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster in MM patients were significantly lower than those of the health controls,while miR-18 1 a/b were exactly the reverse （P〈0.05）.The levels of IL-17,IL-21 and IL-27 were up-regulated in MM patients compared to health controls while IL-22 was down-regulated （P〈0.05）.There was no significant difference of IL-23 between the two groups.The levels of miRNAs and Th17 related cytokines had associated with ISS but not with some clinical parameters （such as gender,age,disease classification）.Higher expression of IL-17,IL-21,IL-23,IL-27,miR-181a/b and lower expression of miR-15a/16,miR-34a,miR-194 and IL-22 were observed in the end stage than the early stage of MM patients （P〈0.05）.There was a significant correlation between miRNAs and Th17 related cytokines.Conclusions Upregulated IL-17,IL-21 and IL-27 may potentially down-regulate the expression of several miRNAs in MM patients.Establishment of the relationship may be useful for understanding the pathogenesis of MM and for clinical diagnosis of the disease.