LncRNA CCAT1 promotes the progression of preeclampsia by regulating CDK4

J.-L. Li, R. Li, Y. Gao, W.-C. Guo, P.-X. Shi, M. Li

Department of Obstetrics, Jining First People’s Hospital, Jining, China. tangd37693082@163.com

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• Obstetrics

OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: LncRNA CCAT1 was highly expressed in preeclampsia and can promote the progression of preeclampsia by inhibiting the expression of CDK4.

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