中文摘要：

目的：探讨microRNA-29c（miR-29c）在胶质瘤中的表达及其对细胞分裂周期蛋白42（CDC42）的调控作用和对细胞增殖的影响。方法：用锁定寡核苷酸原位杂交法和免疫组织化学法检测60例不同级别胶质瘤及10例非肿瘤对照脑组织中miR-29c和CDC42的表达水平，实时荧光定量RT-PCR、Western blot及MTS法分别检测U87MG细胞中miR-29c瞬时表达、CDC42 mRNA和蛋白表达及其对胶质瘤细胞增殖的影响。结果：各级别胶质瘤的miR-29c表达水平均明显低于非肿瘤对照脑组织，且随肿瘤级别升高而显著降低，各组间的差异均有统计学意义（P〈0.001）。而CDC42表达水平则呈相反趋势，其表达水平随胶质瘤良恶性级别增加相应升高，除Ⅰ～Ⅱ级组与非肿瘤对照组之间外，其余各组间的差异均有统计学意义（P〈0.001）。与对照组相比， miR-29c转染组的CDC42 mRNA（P〈0.001）和蛋白表达水平（P〈0.01）均明显降低。miR-29c转染组细胞的增殖能力明显低于U87MG空白对照组和Scr转染组（P〈0.05）。结论：miR-29c是胶质瘤的抑瘤miRNA，其表达水平可作为评价胶质瘤良恶性级别的重要参考指标。miR-29c在胶质瘤中表达减少解除了其对靶基因CDC42转录后水平的抑制作用，并导致肿瘤细胞无限增殖。表明miR-29c表达异常减少可能是引起胶质瘤发生、发展的关键事件。

英文摘要：

Objective：To investigate microRNA-29c （miR-29c） expression and its relationship with CDC42 in gliomas, as well as to observe its effects on the proliferation of the U87MG glioma cell line. Methods：The expression levels of miR-29c and CDC42 were determined by using locked-oligonucleotide-probe in situ hybridization and immunohistochemistry in 10 cases with nontumor control brain tissues and 60 patients with gliomas of 4 pathological grades. Mature mimics of miR-29c and scrambled sequences were chemically synthesized and then transiently transfected into the U87MG glioma cell line. The miR-29c expression level was quantified by using stem-loop real-time quantitative reverse transcription-polymerase chain reaction （qRT-PCR）. The expression levels of CDC42 mRNA and protein, as well as the proliferation capabilities of U87MG, were evaluated by qRT-PCR, Western blot, and MTS assay. Results：Locked-oligonucleotide-probe in situ hybridization showed a downregulation of miR-29c in all glioma samples compared with subjects having nontumor control brain tissues;a continuous decrease was observed as the malignant grade of the tumors increased （P〈0.001）. CDC42 immunohistochemistry exhibited the opposite pattern. The Labeling index （LI%） value of CDC42 was the highest in the WHO grade IV group. All between-group differences, except for that between the WHO grade I-II and nontumor control groups, were statistically significant （P〈0.001）. The miR-29c expression levels in miR-29c transcription groups were significantly higher than those in the blank and Scr control groups （P〈0.001）. Compared with the values for the control groups, the CDC42 mRNA （P〈0.001） and protein （P〈0.01） levels were significantly decreased in the miR-29c transcription groups. The proliferation capabilities of the U87MG glioma cell line in miR-29c transcription groups were significantly lower than those of the control groups at 48 （P〈0.05）, 72 （P〈0.05）, and 96 h （P〈0.001） after transient miR-29c