Abstract

目的探讨miR-223在套细胞淋巴瘤(MCL)患者中的表达及预后意义,并探讨可能的作用机制。方法以21例骨髓受累初治MCL患者为研究对象,以20例健康正常供者为正常对照,采用RQ-PCR法检测miR-223、SOX11 mRNA表达水平。构建过表达miR-223的MCL细胞系Granta519细胞,采用CCK8法和流式细胞术检测其增殖、周期和凋亡水平,采用Western blot法检测其SOX11蛋白表达水平,并利用双荧光素酶报告基因实验验证miR-223的靶基因。结果①21例MCL患者中,男15例,女6例,中位年龄58(37~72)岁,其中17例为中高危组。与正常对照组比较,MCL组患者miR-223表达水平显著下调(1 244.1±1 935.2对14.7±10.5,P<0.001),且其低表达与MCL的IPI评分高危组(P=0.001)、LDH升高(P=0.001)、ECOG评分≥2分(P=0.035)等高危临床特征相关。②以患者组miR-223中位表达水平为阈值,将患者分为高表达组(10例)和低表达组(11例),生存分析结果显示前者的总生存时间较后者延长(36个月对12个月,P=0.021)。③体外实验结果显示,与对照组比较,过表达miR-223的Granta519细胞增殖受抑(96 h时最明显,P<0.001)、处于G2/M期的细胞明显减少(P<0.001)、细胞凋亡比例增加(P<0.001);Granta519细胞的SOX11蛋白表达水平较对照组明显降低。④miR-223可抑制SOX11的3′非翻译区;MCL患者的miR-223与SOX11 mRNA表达水平呈明显负相关(r=−0.81,P<0.001)。结论miR-223在MCL患者中低表达,且与不良预后相关,机制上可能通过靶向SOX11而发挥作用。

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