miR-373在老年多发性骨髓瘤中的作用机制及其临床意义

Mechanism and Clinical Significance of miR-373 In Elderly Patients with Multiple Myeloma

目的:探讨miR-373在多发性骨髓瘤中的作用机制及其临床价值。方法:RT-PCR检测多发性骨髓瘤细胞和正常浆细胞中miR-373的表达水平,同时采用细胞增殖实验、细胞周期与凋亡实验、荧光素酶实验和小鼠成瘤实验分析miR-373的生物学功能。结果:RT-PCR检测发现,MM患者血液样品和多发性骨髓瘤细胞系(H929、MM1S和U266)中miR-373的表达水平比正常浆细胞(对照组)明显降低(P<0.05)。与对照组相比,转染miR-373的U266和H929细胞增殖受到显著抑制(P<0.05);同时转染miR-373的H929细胞周期阻滞在G_0/G_1期并诱导其凋亡(P<0.05)。荧光素酶实验发现,miR-373可显著抑制叉头框蛋白M1(FOXM1)的表达(P<0.05)。小鼠成瘤实验发现,miR-373的过表达通过降低FOXM1水平明显抑制肿瘤生长(P<0.05)。结论:miR-373通过直接靶向FOXM1抑制MM中的肿瘤生长,对治疗MM有重要的临床意义。

Objective： To study the mechanism and clinical value of miR-373 in multiple myeloma.Methods： The expressions of miR-373 in multiple myeloma cells and normal plasma cells were detected by RT-PCR,and the biological function of miR-373 in tumor was analyzed by MTT assay,flow cytometry,luciferase experiment and tumorgenesis experiment.Results： The miR-373 expression levels in MM patients and multiple myeloma cell lines（ H929,MM1S and U266） were significantly lower than that in normal plasma cells detected by using RT-PCR（ P〈0.05）.The proliferations of U266 and H929 cells transfected with miR-373 were significantly suppressed（ P〈0.05）; the cell cycle of H929 cell transfected with miR-373 was arrested in the G0/G1 phase（ P〈0.05） and the cell apoptosis was induced（ P〈0.05）.Luciferase experiment revealed that miR-373 could significantly inhibit the expression of FOXM1（ P〈0.05）.In mouse tumorigenesis experiments,overexpression of miR-373 significantly inhibited tumor growth by decreasing FOXM1 levels（ P〈0.05）.Conclusion： miR-373 inhibits tumor growth in MM by direct targeting FOXM1,thus miR-373 shows an important clinical significance for the treatment of MM.