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作 者:屈晓燕[1] 张森森[1] 吴霜[1] 洪鸣[1] 李建勇[1] 陈丽娟[1] 许家仁[1]
机构地区:[1]南京医科大学第一附属医院、江苏省人民医院血液科,210019
出 处:《中华血液学杂志》2013年第4期332-336,共5页Chinese Journal of Hematology
基 金:国家自然科学基金(81241074、30971294、81071946);江苏省自然科学基金(BK2012485);江苏省“333”工程(BRA2011217);江苏省医学重点人才(RC2011048);江苏省研究生培养创新工程(CXZZ11-0703)
摘 要: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CDl38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),Westernblot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e-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。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 e-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 pa- tients 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). Overexpressiou of miR-92a in MM cell lines induces time-de- pendent down-regulation of e-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.
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