Department of Obstetrics, Jining First People's Hospital, Jining, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1216-1223. doi: 10.26355/eurrev_201803_14461.
Preeclampsia is one of the leading causes of maternal and perinatal deaths. This study mainly explored the mechanism of long non-coding RNA (lncRNA) CCAT1 expression in the placenta of preeclampsia patients and its effect on the progression of preeclampsia.
We used quantitative reverse transcription PCR (qRT‑PCR) to detect the lncRNA CCAT1 expression in 40 preeclampsia and 40 normal pregnancy placenta samples. CCAT1 expression and its relationship with the clinicopathological parameters of preeclampsia was statistically analyzed. The specific small interfering RNA (si-CCAT1) and plasmid (pcDNA-CCAT1) targeting lncRNA CCAT1 were synthesized and transfected into Bew and JEG-3 cells. The CCAT1 expression in Bew and JEG-3 cells was determined by qRT‑PCR. The effect of overexpression and interference of lncRNA CCAT1 on the proliferation of Bew and JEG-3 cells was observed. The effect of CCAT1 on cell cycle was examined by cell cycle assay. The protein expression was accessed by Western blot.
Higher lncRNA CCAT1 expression was found in preeclampsia patients. The systolic blood pressure, diastolic blood pressure and urine protein in preeclampsia patients were significantly higher than those in normal pregnant women. The birth weight of fetus was significantly lower than that of normal pregnant women. However, there was no significant difference in weight and age of patients. According to the CCAT1 expression, preeclampsia patients were assigned into high expression group and low expression group. Higher systolic blood pressure, diastolic blood pressure, and urinary protein levels in CCAT1 high expression group were observed comparing to those in low expression group, while the birth weight in low expression group was significantly higher than the high expression group. In addition, we found that after interference with CCAT1, trophoblast proliferation was significantly increased and cell cycle was significantly accelerated, whereas overexpression of CCAT1 led to the contrary. Western blotting indicated that the expressions of E2F1, cyclin D, CDK2 and CDK4 in BeWo cells were increased after CCAT1 was knocked down. The expressions of E2F1, cyclin D, CDK2 and CDK4 in JEG3 cells were decreased after CCAT1 was overexpressed.
LncRNA CCAT1 was highly expressed in preeclampsia and can promote the progression of preeclampsia by inhibiting the expression of CDK4.
子痫前期是导致孕产妇和围产儿死亡的主要原因之一。本研究主要探讨长链非编码 RNA（lncRNA）CCAT1 在子痫前期患者胎盘组织中的表达机制及其对子痫前期进展的影响。
采用实时定量逆转录 PCR（qRT-PCR）检测 40 例子痫前期和 40 例正常妊娠胎盘组织中 lncRNA CCAT1 的表达情况，统计分析 lncRNA CCAT1 的表达与子痫前期临床病理参数的关系。合成并转染靶向 lncRNA CCAT1 的特异性小干扰 RNA（si-CCAT1）和质粒（pcDNA-CCAT1）。qRT-PCR 检测 Bew 和 JEG-3 细胞中 CCAT1 的表达。观察过表达和干扰 lncRNA CCAT1 对 Bew 和 JEG-3 细胞增殖的影响。细胞周期检测观察 CCAT1 对细胞周期的影响。Western blot 检测蛋白表达。
子痫前期患者 lncRNA CCAT1 表达水平升高。子痫前期患者收缩压、舒张压和尿蛋白均明显高于正常孕妇，胎儿出生体重明显低于正常孕妇，而患者体重和年龄无明显差异。根据 CCAT1 表达情况，将子痫前期患者分为高表达组和低表达组。与低表达组相比，高表达组患者收缩压、舒张压和尿蛋白水平更高，而低表达组出生体重明显高于高表达组。此外，我们发现干扰 CCAT1 后，滋养细胞增殖明显增加，细胞周期明显加快，而过表达 CCAT1 则相反。Western blot 表明，CCAT1 敲低后 BeWo 细胞中 E2F1、cyclin D、CDK2 和 CDK4 的表达增加，而 CCAT1 过表达后 JEG3 细胞中 E2F1、cyclin D、CDK2 和 CDK4 的表达减少。
lncRNA CCAT1 在子痫前期中高表达，可通过抑制 CDK4 的表达促进子痫前期的进展。
