Detection and characterization of placental MicroRNAs in maternal plasma

Detection and characterization of placental MicroRNAs in maternal plasma
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DOI:
10.1373/clinchem.2007.097972
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发表时间:
2008-03-01
期刊:
影响因子:
9.3
通讯作者:
Lo, Y. M. Dennis
Lo, Y. M. Dennis
中科院分区:
医学1区
文献类型:
--
作者:
Chim, Stephen S. C.;Shing, Tristan K. F.;Lo, Y. M. Dennis

文献摘要

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背景:母体血浆中循环胎儿核酸的发现为无创产前诊断开辟了新的可能性。MicroRNAs (miRNAs)是一类小rna,由于其重要的生物学意义,近年来受到了广泛的研究。基因表达的调控作用。由于胎盘来源的核酸被释放到母体血浆中,我们假设胎盘产生的mirna也会被释放到母体血浆中。方法:我们系统地搜索母体血浆中的胎盘mirna,以鉴定胎盘中与母体血细胞中浓度较高的mirna,然后研究母体血浆中这类新型妊娠相关标志物的稳定性和可滤过性。结果:在一组可用于157种确定的mirna的TaqMan检测中,17种mirna在胎盘中的浓度比在母体血细胞中的浓度高10倍,并且在分娩后的母体血浆中检测不到。这些胎盘mirna中最丰富的4种(miR-141、miR-149、miR-299-5p和miR-135b)在妊娠期间可在母体血浆中检测到,在分娩后血浆中检出率降低。miR-141的血浆浓度随着妊娠进展到妊娠晚期而升高。与CSH1[绒毛膜促生长激素I(胎盘乳原)]编码的mRNA相比,miR-141在母体血浆中更加稳定,滤过后其浓度没有降低。结论:我们证实了胎盘mirna在母体血浆中的存在,并提供了一些关于其稳定性和物理性质的信息。这些发现开辟了一类新的分子标记。孕期监测。(c) 2008美国临床化学协会。
BACKGROUND: The discovery of circulating fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. MicroRNAs (miRNAs), a class of small RNAs, have been intensely investigated recently because of their important. regulatory role in gene expression. Because nucleic acids of placental origin are released into maternal plasma, we hypothesized that miRNAs produced by the placenta would also be released into maternal plasma.METHODS: We systematically searched for placental miRNAs in maternal plasma to identify miRNAs that were at high concentrations in placentas compared with maternal blood cells and then investigated the stability and filterability of this novel class of pregnancy-associated markers in maternal plasma.RESULTS: In a panel of TaqMan MicroRNA Assays available for 157 well-established miRNAs, 17 occurred at concentrations > 10-fold higher in the placentas than in maternal blood cells and were undetectable in postdelivery maternal plasma. The 4 most abundant of these placental miRNAs (miR-141, miR-149, miR-299-5p, and miR-135b) were detectable in maternal plasma during pregnancy and showed reduced detection rates in postdelivery plasma. The plasma concentration of miR-141 increased as pregnancy progressed into the third trimester. Compared with mRNA encoded by CSH1 [chorionic somatomammotropin hormone I (placental lactogen)], miR-141 was even more stable in maternal plasma, and its concentration did not decrease after filtration.CONCLUSION: We have demonstrated the existence of placental miRNAs in maternal plasma and provide some information on their stability and physical nature. These findings open up a new class of molecular markers for. pregnancy monitoring. (c) 2008 American Association for Clinical Chemistry.