MicroRNA-126 suppresses the invasion of trophoblast-model JEG-3 cells by targeting LIN28A
MicroRNA-126 suppresses the invasion of trophoblast-model JEG-3 cells by targeting LIN28A
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MicroRNA-126 通过靶向 LIN28A 抑制滋养层模型 JEG-3 细胞的侵袭
DOI：
10.1016/j.bbrc.2021.01.077
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发表时间：
2021
影响因子：
3.1
通讯作者：
Tomi Masatoshi
中科院分区：
文献类型：
--
作者：
Pan Xiaole;Noguchi Saki;Ando Misuzu;Nishimura Tomohiro;Tomi Masatoshi
滋养层浸润不足和滋养层诱导的血管重塑受损是先兆子痫的特征。在这种情况下，血管生成相关的microRNA，miR-126，在先兆子痫胎盘中异常表达，但其在滋养层发育中的作用仍不清楚。本研究以人绒毛膜癌JEG-3细胞为模型，探讨miR-126在滋养层细胞增殖、迁移和侵袭过程中的作用。结合生物信息学分析，有和没有miR-126过表达的JEG-3细胞的mRNA表达谱鉴定出LIN 28 A是miR-126的推定靶标。荧光定量RT-PCR和荧光素酶检测结果与此一致。miR-126在JEG-3细胞中的过表达降低了细胞的侵袭能力，而不影响细胞的增殖或迁移。JEG-3细胞的侵袭性通过用siRNA敲低LIN 28 A和通过miR-126过表达诱导的LIN 28 A下调而显著降低至相似的程度，尽管在siLIN 28 A转染的细胞中LIN 28 A蛋白水平低得多。这些结果表明，miR-126通过靶向LIN 28 A抑制JEG-3细胞侵袭，并表明miR-126介导的LIN 28 A下调可能有助于先兆子痫的发作/恶化。
Inadequate trophoblast invasion and impaired trophoblast-induced vascular remodeling are features of preeclampsia. In this context, an angiogenesis-related microRNA, miR-126, is abnormally expressed in preeclampsia placentas, but its role in trophoblast development remains unclear. The purpose of this study was to investigate the roles of miR-126 in the proliferation, migration, and invasion processes of trophoblast cells using the human choriocarcinoma-derived JEG-3 cell line as a model. The mRNA expression profiling of JEG-3 cells with and without miR-126 overexpression, in combination with bioinformatics analysis, identified LIN28A as a putative target of miR-126. The results of real-time RT-PCR and luciferase assay were consistent with this idea. Overexpression of miR-126 in JEG-3 cells decreased the invasive ability of the cells without affecting proliferation or migration. The invasiveness of JEG-3 cells was significantly reduced to a similar extent by knockdown of LIN28A with siRNA and by miR-126-overexpression-induced downregulation of LIN28A, although the level of LIN28A protein was much lower in the siLIN28A-transfected cells. These results indicate that miR-126 suppresses JEG-3 cell invasion by targeting LIN28A, and suggest that miR-126-mediated downregulation of LIN28A might contribute to the onset/deterioration of preeclampsia.