Department of OB/GYN, University of Florida, Gainesville, FL 32610, USA.
Reprod Sci. 2011 Jan;18(1):46-56. doi: 10.1177/1933719110374115. Epub 2010 Nov 15.
MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability implicated in cell proliferation, apoptosis, and development, whereas their altered expression has been associated with various pathological disorders. The objective of this study was to assess the expression profile of miRNAs and their predicted target genes in placentas from patients with preeclampsia (PC) and preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that 283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the relative expression of 20 miRNAs (P < .05 and ≥ 1.5-fold) and 120 mRNAs (P < .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296-3p, miR-377, miR-483-5p, and miR-493 and a few of their predicted target genes: matrix metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were validated in these cohorts using real-time polymerase chain reaction (PCR), some displaying an inverse correlation with the expression of their predicted target genes. Functional analysis indicated that the products of these genes regulate cellular activities considered critical in normal placental functions and those affected by PC and PT labor. In conclusion, the results provide further evidence that placentas affected by PC and PT labor display an altered expression of a number of miRNAs with potential regulatory functions on the expression of specific target genes whose altered expression and function have been associated with these pregnancy complications.
微小 RNA（miRNA）已成为基因表达稳定性的关键调控因子，参与细胞增殖、凋亡和发育，而其表达的改变与各种病理紊乱有关。本研究旨在评估 miRNA 的表达谱及其预测靶基因在子痫前期（PC）和早产（PT）分娩患者胎盘与正常足月（NT）妊娠胎盘之间的差异。通过对 820 个 miRNA 和 18630 个 mRNA 转录本进行微阵列分析，结果表明，所有胎盘中均表达了其中 283 个 miRNA 和 9119 个 mRNA，其中 20 个 miRNA（P<0.05，且≥1.5 倍）和 120 个 mRNA（P<0.05，且 2 倍截止值）的相对表达在 PT 和 PC 与 NT 相比存在差异。miR-15b、miR-181a、miR-200C、miR-210、miR-296-3p、miR-377、miR-483-5p 和 miR-493 及其部分预测靶基因：基质金属蛋白酶（MMP-1、MMP-9）、解整合素和金属蛋白酶域（ADAM-17、ADAM-30）、金属蛋白酶组织抑制剂 3（TIMP-3）；细胞因子信号转导抑制因子 1（SOCS1）；斯钙素 2（STC2）；促肾上腺皮质激素释放激素（CRH）、CRH 结合蛋白（CRHBP）；内皮素 2（EDN2）在这些队列中使用实时聚合酶链反应（PCR）进行了验证，其中一些与预测靶基因的表达呈负相关。功能分析表明，这些基因的产物调节正常胎盘功能和 PC 及 PT 分娩受影响的细胞活动，这些活动被认为是关键的。总之，结果进一步证明，受 PC 和 PT 分娩影响的胎盘显示出许多 miRNA 的表达发生改变，这些 miRNA 具有对特定靶基因表达的潜在调节功能，其表达和功能与这些妊娠并发症有关。
