The expression profile of circular RNA in placenta of patients with preeclampsia and its correlation with the patient’s condition

doi:10.11958/20221313

Abstract

Abstract:

Objective To analyze expression profile of circular RNA (circRNA) in placenta of patients with preeclampsia and its correlation with the patients' condition. Methods A total of 15 patients with preeclampsia (the preeclampsia group), 25 patients with severe preeclampsia (the severe preeclampsia group), and 30 normal pregnant women (the control group) were selected. Clinical data of patients were collected. 24 h urinary protein levels were detected in each group. Serum STOX1 protein, serum soluble vascular endothelial growth factor receptor 1 (sFlt-1), placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) were detected by enzyme-linked immunosorbent assay. The placental samples were collected after delivery, and the expression of circRNA in placenta was detected. The top three genes with differentially expressed levels of up-regulated and down-regulated genes from high to low were selected for analysis. The correlation of differentially expressed genes with 24 h urinary protein, mean arterial pressure, STOX1, sFlt-1, PLGF and VEGF in pregnant women was analyzed. Multiple linear regression model was used to analyze factors affecting the quantitative level of 24 h urine protein in pregnant women. Results Compared with the control group, there were higher prepregnancy body mass index and mean arterial pressure in the preeclampsia group and the severe preeclampsia group (P<0.05). The 24 h urinary protein quantity, STOX1, sFlt-1, hsa_circ_0014736, hsa_circ_0015383 and hsa_circ_0004904 expression levels in placenta were increased gradually in the control group, the preeclampsia group and the severe preeclampsia group. The expression levels of hsa_circ_0063517, hsa_circ_0007121 and hsa_circ_0003171 were decreased gradually (P<0.05). Values of hsa_circ_0014736, hsa_circ_0015383 and hsa_circ_0004904 were positively correlated with mean arterial pressure, 24 h urinary protein quantity, STOX1 and sFlt-1 in the preeclampsia group and the severe preeclampsia group respectively. They were negatively correlated with VEGF and PLGF (P<0.05), while hsa_circ_0063517, hsa_circ_0007121 and hsa_circ_0003171 were negatively correlated with clinical features (P<0.05). Multiple linear regression analysis showed that hsa_circ_0015383 had positive linear correlation with 24 h urinary protein quantification in pregnant women, and hsa_circ_0063517 and hsa_circ_0007121 had negative linear correlation with 24 h urinary protein quantification in pregnant women (P<0.05). Conclusion The expression levels of hsa_circ_0063517 and hsa_circ_0007121 in placenta are down-regulated in preeclampsia pregnant women, and expression levels of hsa_circ_0015383 are up-regulated, which is closely related to the patient's condition.

Key words: pre-eclampsia, placenta, RNA, circular, vascular endothelial growth factor receptor-1, placenta growth factor, vascular endothelial growth factors, 24 h urine protein quantification

CLC Number:

R446.8

Figures/Tables 5

References 18

[1]	SNELL K, ALLOTEY J, SMUK M, et al. External validation of prognostic models predicting pre-eclampsia:individual participant data meta-analysis[J]. BMC Med, 2020, 18(1):302. doi:10.1186/s12916-020-01766-9.
[2]	TESFA E, NIBRET E, MUNSHEA A. Maternal lipid profile and risk of pre-eclampsia in African pregnant women:A systematic review and meta-analysis[J]. PLoS One, 2020, 15(12):e0243538. doi:10.1371/journal.pone.0243538.
[3]	BERGMAN L, BERGMAN K, LANGENEGGER E, et al. PROVE-pre-eclampsia obstetric adverse events:Establishment of a biobank and database for pre-eclampsia[J]. Cells, 2021, 10(4):959. doi:10.3390/cells10040959.
[4]	DAI X, CHEN C, YANG Q, et al. Exosomal circRNA_100284 from arsenite-transformed cells,via microRNA-217 regulation of EZH2,is involved in the malignant transformation of human hepatic cells by accelerating the cell cycle and promoting cell proliferation[J]. Cell Death Dis, 2018, 9(5):454. doi:10.1038/s41419-018-0485-1.
[5]	CAO M, WEN J, BU C, et al. Differential circular RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients[J]. BMC Pregnancy Childbirth, 2021, 21(1):303. doi:10.1186/s12884-021-03777-7.
[6]	王思远, 张国英, 韩平. 环状RNA在子痫前期发病机制和预测中的研究进展[J]. 现代妇产科进展, 2019, 28(8):634-636.
	WANG S Y, ZHANG G Y, HAN P. Research progress of cyclic RNA in pathogenesis and prediction of preeclampsia[J]. Prog Obstet Gynecol, 2019, 28(8):634-636. doi:10.13283/j.cnki.xdfckjz.2019.08.018.
[7]	中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2020)[J]. 中华妇产科杂志, 2020, 55(4):227-238.
	Department of Gestational Hypertension,Department of Obstetrics and Gynecology,Chinese Medical Association. Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy:A clinical practice guideline in China(2020)[J]. Chin J Obstet Gynecol, 2020, 55(4):227-238. doi:10.3760/cma.j.cn112141-20200114-00039.
[8]	SHAN L, HOU X. Circular RNA hsa_circ_0026552 inhibits the proliferation, migration and invasion of trophoblast cells via the miR-331-3p/TGF-βR1 axis in pre-eclampsia[J]. Mol Med Rep, 2021, 24(5):798. doi:10.3892/mmr.2021.12438.
[9]	高明明, 俞兆儿, 姚丹, 等. 环状RNA hsa_circ_0005579在子痫前期患者胎盘中的表达及对滋养层细胞增殖、迁移及侵袭的影响[J]. 南京医科大学学报(自然科学版), 2022, 42(8):1112-1118.
	GAO M M, YU Z E, YAO D, et al. The expression of circular RNA hsa_circ_0005579 in the placenta of patients withpreeclampsia and its effect on the proliferation,migration and invasion of trophoblast cells[J]. Journal of Nanjing Medical University(Natural Sciences), 2022, 42(8):1112-1118. doi:10.7655/NYDXBNS20220810.
[10]	陈维, 白宇翔, 饶海英, 等. 子痫前期胎盘组织环状RNA表达谱的鉴定、验证与分析[J]. 重庆医科大学学报, 2020, 45(5):620-626.
	CHEN W, BAI Y X, RAO H Y, et al. Identification and analysis profiles of circular RNAs in preeclamptic placenta[J]. Journal of Chongqing Medical University, 2020, 45(5):620-626. doi:10.13406/j.cnki.cyxb.002367.
[11]	BAI Y, RAO H, CHEN W, et al. Profiles of circular RNAs in human placenta and their potential roles related to preeclampsia[J]. Biol Reprod, 2018, 98(5):705-712. doi:10.1093/biolre/ioy034.
[12]	GAI S, SUN L, WANG H, et al. Circular RNA hsa_circ_0007121 regulates proliferation,migration,invasion,and epithelial-mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia[J]. Open Med(Wars), 2020, 15(1):1061-1071. doi:10.1515/med-2020-0230.
[13]	LI W, YU N, FAN L, et al. Circ_0063517 acts as ceRNA,targeting the miR-31-5p-ETBR axis to regulate angiogenesis of vascular endothelial cells in preeclampsia[J]. Life Sci, 2020, 244:117306. doi:10.1016/j.lfs.2020.117306.
[14]	NELSON D S, VAN HALTEREN A, QUISPEL W T, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis[J]. Genes Chromosomes Cancer, 2015, 54(6):361-368. doi:10.1002/gcc.22247.
[15]	周晓. 子痫前期胎盘组织环状RNA表达谱分析及初步应用研究[D]. 南昌: 南昌大学, 2020.
	ZHOU X. Involvement of circular RNAs in preeclampsia and mechanistic study[D]. Nanchang: Nanchang University, 2020.
[16]	LI L, PENG W, ZHOU Q, et al. LRP6 regulates Rab7-mediated autophagy through the Wnt/β-catenin pathway to modulate trophoblast cell migration and invasion[J]. J Cell Biochem, 2020, 121(2):1599-1609. doi:10.1002/jcb.29394.
[17]	刘筠, 李萍, 张敏. 子痫前期患者血清STOX1、sFlt-1与病情及妊娠结局的关系[J]. 中国现代医学杂志, 2019, 29(20):96-100.
	LIU Y, LI P, ZHANG M. Relationship between serum STOX1,sFlt-1 and state of illness and pregnancy outcome in patients with preeclampsia[J]. China Journal of Modern Medicine, 2019, 29(20):96-100. doi:10.3969/j.issn.1005-8982.2019.20.019.
[18]	禹红, 吴迪, 汪新妮. 妊娠高血压患者孕晚期血清PLGF、VEGF与胎儿生长受限的关系[J]. 中国优生与遗传杂志, 2022, 30(9):1550-1554.
	YU H, WU D, WANG X N. Relationship between serum PLGF,VEGF and fetal growth restriction in patients with gestational hypertension in the third trimester of pregnancy[J]. Chinese Journal of Birth Health & Heredity, 2022, 30(9):1550-1554. doi:10.13404/j.cnki.cjbhh.2022.09.005.

组别	n	年龄（岁）	孕次（次）	产次		孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
组别	n	年龄（岁）	孕次（次）	初产妇	经产妇	孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
对照组	30	28.01±4.53	1.28±0.37	13	17	33.91±3.25	23.78±2.36	95.01±3.76
子痫前期组	15	28.68±4.98	1.45±0.36	4	11	32.98±2.97	25.36±2.54^a	100.83±6.72^a
重度子痫前期组	25	27.39±4.45	1.43±0.41	9	16	33.14±3.02	25.89±3.36^a	106.78±8.46^ab
F或χ²		0.376	1.464	1.212		0.622	4.181^＊	22.961^＊＊

组别	n	年龄（岁）	孕次（次）	产次		孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
组别	n	年龄（岁）	孕次（次）	初产妇	经产妇	孕周（周）	BMI （kg/m²）	平均动脉压（mmHg）
对照组	30	28.01±4.53	1.28±0.37	13	17	33.91±3.25	23.78±2.36	95.01±3.76
子痫前期组	15	28.68±4.98	1.45±0.36	4	11	32.98±2.97	25.36±2.54^a	100.83±6.72^a
重度子痫前期组	25	27.39±4.45	1.43±0.41	9	16	33.14±3.02	25.89±3.36^a	106.78±8.46^ab
F或χ²		0.376	1.464	1.212		0.622	4.181^＊	22.961^＊＊

组别	n	24 h尿蛋白定量（g）	STOX1（ng/L）	sFlt-1（ng/L）	VEGF（ng/L）	PLGF（pg/L）
对照组	30	0.09±0.01	40.67±5.13	203.54±65.28	232.73±25.76	511.23±79.21
子痫前期组	15	1.28±0.33^a	44.39±6.28^a	255.82±71.34^a	187.12±20.89^a	461.54±62.79^a
重度子痫前期组	25	4.43±1.21^ab	49.41±7.39^ab	298.42±79.48^ab	151.37±18.26^ab	413.64±53.02^ab
F		241.269^＊＊	13.298^＊＊	11.966^＊＊	91.537^＊＊	14.319^＊＊

组别	n	24 h尿蛋白定量（g）	STOX1（ng/L）	sFlt-1（ng/L）	VEGF（ng/L）	PLGF（pg/L）
对照组	30	0.09±0.01	40.67±5.13	203.54±65.28	232.73±25.76	511.23±79.21
子痫前期组	15	1.28±0.33^a	44.39±6.28^a	255.82±71.34^a	187.12±20.89^a	461.54±62.79^a
重度子痫前期组	25	4.43±1.21^ab	49.41±7.39^ab	298.42±79.48^ab	151.37±18.26^ab	413.64±53.02^ab
F		241.269^＊＊	13.298^＊＊	11.966^＊＊	91.537^＊＊	14.319^＊＊

组别	n	hsa_circ_0014736	hsa_circ_0015383	hsa_circ_0004904	hsa_circ_0063517	hsa_circ_0007121	hsa_circ_0003171
对照组	30	0.81±0.15	0.83±0.17	0.87±0.23	1.07±0.23	1.21±0.19	1.19±0.23
子痫前期组	15	1.13±0.17^a	1.02±0.19^a	1.12±0.27^a	0.87±0.16^a	0.76±0.15^a	1.01±0.18^a
重度子痫前期组	25	1.53±0.19^ab	1.48±0.23^ab	1.33±0.34^ab	0.72±0.11^ab	0.43±0.12^ab	0.89±0.17^ab
F		123.127^＊＊	75.541^＊＊	18.263^＊＊	25.938^＊＊	164.876^＊＊	15.614^＊＊