MicroRNA-34a inhibits human trophoblast cell invasion by targeting MYC.
MicroRNA-34a inhibits human trophoblast cell invasion by targeting MYC.
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MicroRNA-34a 通过靶向 MYC 抑制人滋养层细胞侵袭。
DOI：
10.1186/s12860-015-0068-2
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发表时间：
2015-09-03
期刊：
影响因子：
--
通讯作者：
Meng T
中科院分区：
文献类型：
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作者：
Sun M;Chen H;Liu J;Tong C;Meng T
子痫前期是妊娠的主要疾病之一，其特点是滋养细胞侵袭不足，滋养细胞介导的胎盘血管重构存在缺陷。MicroRNA-34a （miR-34a）已被发现在子痫前期患者的胎盘中异常表达，但其在胎盘发育和子痫前期发病中的作用尚不清楚。采用real - time-PCR检测20例子痫前期患者和20例健康受试者胎盘中miR-34a水平，发现miR-34a在子痫前期胎盘中显著升高。进一步，通过在JEG-3滋养细胞中过表达miR-34a，研究miR-34a在滋养细胞中的功能。在JEG-3细胞中过表达miR-34a可抑制细胞增殖、迁移和侵袭。此外，miR-34a的表达升高降低了内源性和异位MYC的表达。此外，我们通过双荧光素酶报告基因实验发现，MYC mRNA是JEG-3细胞中miR-34a的直接靶点，并发现miR-34a靶向下调MYC表达可显著降低JEG-3细胞的侵袭性。我们的研究结果为miR-34a在滋养细胞生物学中的多种功能提供了初步证据，并提示miR-34a通过直接靶向MYC抑制滋养细胞的侵袭。
Preeclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. MicroRNA-34a (miR-34a) has been found to be aberrantly expressed in the placentas of preeclamptic patients, yet its role in placental development and in the pathogenesis of preeclampsia remains elusive. The levels of miR-34a in the placentas of 20 preeclamptic patients and 20 healthy subjects were determined by real time-PCR, and miR-34a was found significantly elevated in the preeclamptic placentas. Further, the function of miR-34a in trophoblast cells was investigated by overexpressing miR-34a in JEG-3 trophoblast cell line. Overexpression of miR-34a in JEG-3 cells inhibited cell proliferation, migration and invasion. In addition, elevated expression of miR-34a reduced the expression of both endogenous and ectopic MYC. Moreover, we identified that MYC mRNA was a direct target of miR-34a in JEG-3 cells by dual luciferase reporter assay, and found that downregulation of MYC expression by miR-34a targeting significantly reduced the invasiveness of JEG-3 cells. Our findings provide preliminary evidence for the diverse functions of miR-34a in trophoblast biology, and suggest that miR-34a suppresses trophoblast invasion by directly targeting MYC.