Long Non-Coding RNA Uc.187 Is Upregulated in Preeclampsia and Modulates Proliferation, Apoptosis, and Invasion of HTR-8/SVneo Trophoblast Cells
Long Non-Coding RNA Uc.187 Is Upregulated in Preeclampsia and Modulates Proliferation, Apoptosis, and Invasion of HTR-8/SVneo Trophoblast Cells
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长非编码 RNA Uc.187 在先兆子痫中上调并调节 HTR-8/SVneo 滋养层细胞的增殖、凋亡和侵袭
DOI：
10.1002/jcb.25805
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发表时间：
2017-06-01
影响因子：
4
通讯作者：
Jia, Ruizhe
中科院分区：
文献类型：
--
作者：
Cao, Chunyu;Li, Jingyun;Jia, Ruizhe
在我们前期研究中利用基因芯片筛选的子痫前期相关的长非编码RNA（longnon-cordingRNAs，lncRNAs）中，uc.187因其在不同物种间的高度保守性以及与子痫前期（preeclampsia，PE）的显著正相关性而引起我们的关注。文献和生物信息学分析表明，lncRNA uc. 187可能与细胞生长、侵袭和凋亡有关。UC的表达。通过实时逆转录聚合酶链反应（qRT-PCR）评估重度先兆子痫胎盘（n = 31）和正常胎盘（n = 18）中的187。我们构建了沉默慢病毒载体（uc. 187 siRNA），探讨uc的生物学功能。187在体外HTR-8/SVneo滋养层细胞的发育和进展中的作用。此外，我们利用CCK 8分析，transwell侵袭试验和流式细胞术来确定uc的作用。187在HTR-8/SVneo滋养层细胞的增殖、侵袭和凋亡中的作用。Western blot检测增殖相关蛋白（PCNA、Ki 67）、侵袭相关蛋白（MMP-2/-9和TIMP-1）、凋亡相关蛋白（caspase-3、Bcl-2）。结果表明，在体外培养条件下，uc表达明显上调。187在先兆子痫胎盘组织中的表达。此外，UC。187沉默增强细胞增殖和侵袭，并降低细胞凋亡反应。综上所述，我们的研究结果首次表明，lncRNA表达异常uc。187可能导致HTR-8/SVneo细胞的异常生物学行为。因此，我们建议UC。187作为一种新的lncRNA分子，可能有助于PE的发展，并可能代表这种疾病的潜在诊断和治疗靶点。(C)2016 Wiley Periodicals，Inc.
Among the preeclampsia-related long non-cording RNAs (lncRNAs) screened with a gene chip in our preliminary study, uc.187 attracted our attention because of its high conservation across different species and significant positive correlation with preeclampsia (PE). The literature and bioinformatics analysis suggested that lncRNA uc. 187 might be associated with cell growth, invasion, and apoptosis. The expression of uc. 187 in severe preeclamptic placentas (n = 31) and normal placentas (n = 18) was evaluated by real-time reverse transcription polymerase chain reaction (qRT-PCR). We constructed a silencing lentivirus vector (uc. 187 siRNA) to explore the biological function of uc. 187 in the development and progression of HTR-8/SVneo trophoblast cells in vitro. Furthermore, we utilized CCK8 analysis, a transwell invasion assay, and flow cytometry to determine the role of uc. 187 in the proliferation, invasion, and apoptosis of HTR-8/SVneo trophoblast cells. The proteins related to proliferation (PCNA, Ki67), invasion (MMP-2/-9 and TIMP-1), and apoptosis (caspase-3, Bcl-2) were evaluated with a Western blot assay. The results showed that there was an obvious upregulation of uc. 187 expression in preeclamptic placental tissues. In addition, uc. 187 silencing enhanced cell proliferation and invasion and reduced the cellular apoptotic response. Taken together, our findings suggest for the first time that abnormal expression of lncRNA uc. 187 may lead to the aberrant biological behavior of HTR-8/SVneo cells. Therefore, we propose uc. 187 as a novel lncRNA molecule that might contribute to the development of PE and might represent a potential diagnostic and therapeutic target for this disease. (C) 2016 Wiley Periodicals, Inc.