Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids.
Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids.
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DOI：
10.1111/j.1582-4934.2007.00207.x
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发表时间：
2008-01
影响因子：
5.3
通讯作者：
Chegini N
中科院分区：
文献类型：
--
作者：
Pan Q;Luo X;Chegini N
考虑到microRNAs（miRNAs）作为mRNA稳定性关键调节因子的新兴作用，我们评估了它们在配对的子宫肌层和平滑肌瘤中的表达谱，（MSMC和LSMC）、自发转化的平滑肌瘤平滑肌细胞（T-LSMC）和SK-LMS-1，利用基因芯片和真实的时间PCR技术对平滑肌肉瘤细胞株进行检测，通过对385个miRNAs表达值的整体标准化和统计学分析，（方差分析），91个miRNAs在子宫肌层中表达高于阈值水平，在平滑肌瘤、MSMC、LSMC、T-LSMC和SK-LMS-1中数量逐渐下降。（P<0.05）。我们筛选并验证了miR-20 a、miR-21、miR-26 a、miR-18 a、miR-206、miR-181 a和miR-142- 5 p在组织和细胞中的表达存在差异（P<0.05）.用17β雌二醇和醋酸甲羟孕酮（10 - 8 M）处理MSMC和LSMC，或ICI-182780和RU-486（10− 6 M）导致这些miRNA的差异调节结论：子宫肌层和子宫肌瘤组织中大量miRNAs的表达随着其由正常平滑肌细胞向平滑肌细胞的进行性变异，提示卵巢激素对miRNAs表达的调控通过基因表达的稳定性在平滑肌瘤的发病机制中起关键作用。
Given the emerging roles of microRNAs (miRNAs) as key regulator of mRNA stability we assessed their expression profile in paired myometrium and leiomyoma, their isolated smooth muscle cells (MSMC and LSMC), a spontaneously transformed leiomyoma smooth muscle cells (T-LSMC) and SK-LMS-1, a leiomyosarcoma cell line using microarray and real time PCR.Based on global normalization of expression values of 385 miRNAs and statistical analysis (anova), 91 miRNAs were expressed above the threshold levels in myometrium, with a progressive decline in numbers in leiomyomas, MSMC, LSMC, T-LSMC and SK-LMS-1 (P<0.05).We selected and validated the expression of miR-20a, miR-21, miR-26a, miR-18a, miR-206, miR-181a and miR-142–5p and found their differential expression in tissue and cell-specific manners (P<0.05).Treatments of MSMC and LSMC with 17β estradiol and medroxyprogesterone acetate (10−8M), or ICI-182780 and RU-486 (10−6M) resulted in differential regulation of these miRNAs (P<0.05).In conclusion, the expression of a number of miRNAs in myometrium and leiomyoma with their progressive aberrant from normal MSMC into LSMC, transformed and cancerous stage, suggests that miRNAs and their regulation by ovarian steroids play a key role in pathogenesis of leiomyoma through gene expression stability.
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