Objective: To investigate the relationship between the expression level of microRNA 92a (miR-92a) and del(13q14) and the prognosis of MM patients, and to explore the pathway that miR-92a involved.
Methods: Bone marrow samples from 53 newly diagnosed MM patients were collected, del(13q14) was analyzed by interphase fluorescence in situ hybridization in sorted CD138 positive plasma cell. The expression of miR-92a in plasma cells was measured by quantitative real-time PCR. The expression of c-jun was detected by Western blot in miR-92a transfected MM cell lines (LP-1, U266 and JJN3).
Results: Of the 53 MM patients, del(13q14) was detected in 31 (58.4%) patients. The median levels of miR-92a in MM patients with or without del(13q14) were 27.36±2.61 and 21.87±15.98, respectively (P>0.05). With the median follow-up of 13.5 (0.5-72.5) months, the median duration of progression-free survival of patients with high expression level of miR-92a was significantly shorter than those with low expression level of miR-92a (4.5 months vs 14.0 months, P=0.006). Overexpression of miR-92a in MM cell lines induces time-dependent down-regulation of c-jun.
Conclusions: High expression of miR-92a was associated with poor prognosis in MM patients. The expression level of miR-92a was not associated with del(13q14), and the effect of miR-92a on the progress of MM might be involved in c-jun pathway.
目的 探讨多发性骨髓瘤（MM）患者微小RNA-92a（miR-92a）的表达水平及其与染色体del(13q14)和患者预后的关系，并进一步探索miR-92a作用的信号通路。方法 收集53例初诊MM患者骨髓标本，用CD138磁珠分选浆细胞，然后用间期荧光原位杂交技术检测染色体del(13q14)情况；用实时定量 PCR检测浆细胞中miR-92a的表达；用miR-92a前体转染MM细胞株（LP-1、U266和JJN3），Western blot法检测c-jun蛋白表达水平。结果 53例MM患者中31例（58.5%）染色体del(13q14)阳性；伴有和不伴有del(13q14)的患者miR-92a相对中位表达水平分别为27.36±2.61和21.87±15.98，两者差异无统计学意义（P>0.05）。中位随访13.5（0.5~72.5）个月，miR-92a高表达的患者中位无进展生存期明显短于低表达者（4.5个月对14.0个月，P=0.006）。转染miR-92a前体后，MM细胞株（LP-1、U266和JJN3）中c-jun蛋白表达水平呈时间依赖性下降。结论 miR-92a高表达的MM患者预后差，miR-92a表达水平与del(13q14)无相关性，miR-92a有可能通过c-jun途径影响MM的疾病过程。