Dong Xiaorui, Zhang Yina, Chen Xixi, Xue Mengling
Department of Obstetrics, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.
J Obstet Gynaecol Res. 2020 Aug;46(8):1298-1309. doi: 10.1111/jog.14344. Epub 2020 Jun 17.
Pre-eclampsia (PE) is the usual complication during pregnancy. Long noncoding RNAs are essential regulatory factors in many diseases. Nevertheless, the role of LINC00511 in the development of PE has not been fully elucidated.
The expression of LINC00511, homeobox protein A7 (HOXA7) and miR-31-5p was determined by quantitative real-time polymerase chain reaction. The levels of HOXA7 protein and autophagy-related proteins were measured by western blot analysis. Besides, cell proliferation was evaluated using cell counting kit 8 and colony formation assays. The apoptosis and invasion of cells were detected via flow cytometry and transwell assay, respectively. Further, the interaction between miR-31-5p and LINC00511 or HOXA7 was confirmed by dual-luciferase reporter assay.
The LINC00511 and HOXA7 expression levels were decreased in placental tissues of PE patients, and the expression levels of both were positively correlated. LINC00511 knockdown suppressed proliferation, invasion and autophagy, while enhanced apoptosis in trophoblast cells. Meanwhile, the elevated HOXA7 expression promoted proliferation, invasion, autophagy, and inhibited the apoptosis of trophoblast cells. Besides, overexpression of HOXA7 also could reverse the effect of LINC00511 knockdown on the biological function of trophoblast cells. Further experiments confirmed that miR-31-5p could be sponged by LINC00511 and could target HOXA7. Also, miR-31-5p mimic could invert the promoting effect of LINC00511 overexpression on the biological function of trophoblast cells.
LINC00511 expression was crucial for maintaining the normal function of trophoblast cells, and the decreased its expression might promote the progress of PE, which might provide some theoretical strategies for reducing the development of PE.
子痫前期（PE）是孕期常见并发症。长链非编码RNA是许多疾病中的重要调控因子。然而，LINC00511在PE发生发展中的作用尚未完全阐明。
采用定量实时聚合酶链反应检测LINC00511、同源框蛋白A7（HOXA7）和miR-31-5p的表达。通过蛋白质免疫印迹分析检测HOXA7蛋白和自噬相关蛋白的水平。此外，使用细胞计数试剂盒8和集落形成试验评估细胞增殖。分别通过流式细胞术和Transwell试验检测细胞凋亡和侵袭情况。进一步通过双荧光素酶报告基因试验证实miR-31-5p与LINC00511或HOXA7之间的相互作用。
PE患者胎盘组织中LINC00511和HOXA7表达水平降低，且二者表达水平呈正相关。敲低LINC00511可抑制滋养层细胞增殖、侵袭和自噬，同时增强细胞凋亡。同时，HOXA7表达升高可促进滋养层细胞增殖、侵袭、自噬并抑制细胞凋亡。此外，HOXA7过表达也可逆转LINC00511敲低对滋养层细胞生物学功能的影响。进一步实验证实，LINC00511可吸附miR-31-5p，且miR-31-5p可靶向HOXA7。此外，miR-31-5p模拟物可逆转LINC00511过表达对滋养层细胞生物学功能的促进作用。
LINC00511表达对维持滋养层细胞正常功能至关重要，其表达降低可能促进PE进展，这可能为减少PE发生提供一些理论策略。
