Expression levels and clinical significance of miR-1227-3p and miR-212-3p in serum and placenta in puerperas with fetal growth restriction

doi:10.11958/20250839

Abstract

Abstract:

Objective To investigate the expression levels and clinical significance of serum and placental microRNA (miR) -1227-3p and miR-212-3p in puerperas with fetal growth restriction (FGR). Methods A total of 120 puerperas diagnosed with FGR and completed delivery in our hospital were included as the study group. Patients were assigned into the mild group (n=72) and the severe group (n=48) according to the severity of their condition. Another 120 healthy puerperas who underwent prenatal check ups and delivered during the same period in our hospital were included as the control group. QRT-PCR was used to detect serum and placental miR-1227-3p and miR-212-3p. The pregnancy outcomes of both groups were recorded, including neonatal weight, 1min Apgar score, placental weight and placental volume. Results Serum and placental miR-1227-3p expression levels, neonatal weight, 1 min Apgar score, placental weight and placental volume were significantly lower in the study group than those of the control group (P<0.05), while serum and placental miR-212-3p expression levels were significantly higher than those of the control group (P<0.05). The expression levels of miR-1227-3p in serum and placenta of the severe group were obviously lower than those of the mild group (P<0.05), while the expression level of miR-212-3p was obviously higher than those of the mild group (P<0.05). The expression levels of miR-1227-3p in serum and placenta were positively correlated with neonatal weight, 1 min Apgar score, placental weight and placental volume, and the expression levels of miR-212-3p in serum and placenta were negatively correlated with the above indicators (P<0.05). Multivariate Logistic regression analysis revealed that elevated serum and placental miR-212-3p levels were risk factors for FGR (P<0.05), and increased serum and placental miR-1227-3p, neonatal weight, 1 min Apgar, placental weight and placental volume were protective factors (P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the diagnostic value of combined detection of serum and placenta miR-1227-3p and miR-212-3p levels for FGR was better than that of single diagnosis. Conclusion The combined detection of miR-1227-3p and miR-212-3p in serum and placenta of FGR puerperas has certain value in the clinical diagnosis of FGR.

Key words: fetal growth retardation, placenta, serum, pregnancy outcome, miR-1227-3p, miR-212-3p

CLC Number:

R714.43

Figures/Tables 11

References 22

[1]	陈瑞欣, 漆洪波, 刘兴会. 2021年美国妇产科医师协会胎儿生长受限指南解读[J]. 实用妇产科杂志, 2021, 37(12):907-909.
	CHEN R X, QI H B, LIU X H. Interpretation of the 2021 American College of Obstetricians and Gynaecologists guidelines on fetal growth restriction[J]. Journal of Practical Obstetrics and Gynaecology, 2021, 37(12):907-909.
[2]	American College of Obstetricians and Gynecologists' Committee on Practice Bulletins— Obstetrics and the Society for Maternal-Fetal Medicine. ACOG Practice Bulletin No. 204:Fetal Growth Restriction[J]. Obstet Gynecol, 2019, 133(2):e97-e109. doi:10.1097/AOG.00000000000003070.
[3]	WESTBY A, MILLER L. Fetal growth restriction before and after birth[J]. Am Fam Physician, 2021, 104(5):486-492.
[4]	范丽敏, 张雪葳, 刘培林, 等. GDM孕妇孕晚期胎儿脐动脉超声参数、血清FFA及PL在FGR诊断中的应用[J]. 影像科学与光化学, 2022, 40(4):986-990.
	FAN L M, ZHANG X W, LIU P L, et al. Fetal umbilical artery ultrasound parameters,serum FFA and PL in the diagnosis of FGR during late pregnancy in pregnant women with GDM[J]. Imaging Science and Photochemistry, 2022, 40(4):986-990. doi:10.7517/issn.1674-0475.220141.
[5]	QIN K, XIE X, TANG W, et al. Non-coding RNAs to regulate cardiomyocyte proliferation:A new trend in therapeutic cardiac regeneration[J]. Front Cardiovasc Med, 2022, 9(1):944393-944399. doi:10.3389/fcvm.2022.944393.
[6]	MORI M A, LUDWIG R G, GARCIA-MARTIN R, et al. Extracellular miRNAs:from biomarkers to mediators of physiology and disease[J]. Cell Metab, 2019, 30(4):656-673. doi:10.1016/j.cmet.2019.07.011.
[7]	CUI J, KANG X, SHAN Y, et al. miR-1227-3p participates in the development of fetal growth restriction via regulating trophoblast cell proliferation and apoptosis[J]. Sci Rep, 2022, 12(1):6374-6379. doi:10.1038/s41598-022-10127-w.
[8]	YU L, SUN Y, CHU Z. MiR-212-3p promotes proliferation and migration of trophoblast in fetal growth restriction by targeting placental growth factor[J]. Bioengineered, 2021, 12(1):5655-5663. doi:10.1080/21655979.2021.1967069.
[9]	中华医学会围产医学分会胎儿医学学组, 中华医学会妇产科学分会产科学组. 胎儿生长受限专家共识(2019版)[J]. 中华围产医学杂志, 2019, 22(6):361-380.
	Fetal Medicine Group of the Chinese Medical Association Branch of Perinatal Medicine, Obstetrics and Gynaecology Group of the Chinese Medical Association Branch of Obstetrics and Gynaecology. Expert consensus on fetal growth restriction(2019 edition)[J]. Chinese Journal of Perinatal Medicine, 2019, 22(6):361-380. doi:10.3760/cma.j.issn.1007-9408.2019.06.001.
[10]	MARTINS J G, BIGGIO J R, ABUHAMAD A. Society for Maternal-Fetal Medicine Consult Series #52:Diagnosis and management of fetal growth restriction:(Replaces Clinical Guideline Number 3,April 2012)[J]. Am J Obstet Gynecol, 2020, 223(4):B2-B17. doi:10.1016/j.ajog.2020.05.010.
[11]	陈振烈, 曹羽明, 张铭, 等. 白细胞介素-1β在胎儿生长受限孕妇胎盘组织中的表达及其意义[J]. 实用妇产科杂志, 2022, 38(9):699-704.
	CHEN Z L, CAO Y M, ZHANG M, et al. Expression of interleukin-1β in placental tissue of pregnant women with fetal growth restriction and its significance[J]. Journal of Practical Obstetrics and Gynaecology, 2022, 38(9):699-704.
[12]	王婵敏, 郜蕊, 黄丽华, 等. 胎儿生长受限营养干预效果不良的影响因素分析[J]. 华南预防医学, 2020, 46(2):111-115.
	WANG C M, GAO R, HUANG L H, et al. Analysis of factors affecting the poor outcome of nutritional intervention for fetal growth restriction[J]. South China Preventive Medicine, 2020, 46(2):111-115. doi:10.12183/j.scjpm.2020.0111.
[13]	刘洋, 李超, 乔炳龙, 等. 血清妊娠相关蛋白A联合子宫动脉多普勒超声在妊娠早期预测胎儿生长受限的临床价值[J]. 解放军医学院学报, 2021, 42(1):53-56.
	LIU Y, LI C, QIAO B L, et al. Clinical value of serum pregnancy-associated protein A combined with uterine artery Doppler ultrasound in predicting fetal growth restriction in early pregnancy[J]. Journal of PLA Medical College, 2021, 42(1):53-56. doi:10.3969/j.issn.2095-5227.2021.01.012.
[14]	RAHAT B, HAMID A, BAGGA R, et al. Folic acid levels during pregnancy regulate trophoblast invasive behavior and the possible development of preeclampsia[J]. Front Nutr, 2022, 9(1):847136-847142. doi:10.3389/fnut.2022.847136.
[15]	HUANG Z, ZHU L, ZHANG Q, et al. Circular RNA hsa-circ-0005238 enhances trophoblast migration,invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis[J]. Front Med(Lausanne), 2022, 9(1):943885-943889. doi:10.3389/fmed.2022.943885.
[16]	ZHAO Y, XU L, WANG X, et al. A novel prognostic mRNA/miRNA signature for esophageal cancer and its immune landscape in cancer progression[J]. Mol Oncol, 2021, 15(4):1088-1109. doi:10.1002/1878-0261.12902.
[17]	BAKER B C, LUI S, LORNE I, et al. Sexually dimorphic patterns in maternal circulating micro RNAs in pregnancies complicated by fetal growth restriction[J]. Biol Sex Differ, 2021, 12(1):61-67. doi:10.1186/s13293-021-00405-z.
[18]	YANG C, CAI X, YU M, et al. Long noncoding RNA OR3A4 promotes the proliferation and invasion of osteosarcoma cells by sponging miR-1227-5p[J]. J Bone Oncol, 2020, 21(1):100278-100286. doi:10.1016/j.jbo.2020.100278.
[19]	LV Y, LV M, JI X, et al. Down-regulated expressed protein HMGB3 inhibits proliferation and migration,promotes apoptosis in the placentas of fetal growth restriction[J]. Int J Biochem Cell Biol, 2019, 107(1):69-76. doi:10.1016/j.biocel.2018.11.007.
[20]	HOWE C G, FOLEY H B, KENNEDY E M, et al. Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study[J]. Epigenetics, 2022, 17(3):269-285. doi:0.1080/15592294.2021.1899887.
[21]	TANG R, ZHANG Z, HAN W. CircLRRK1 targets miR-223-3p to inhibit the proliferation,migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway[J]. Placenta, 2021, 104(1):110-118. doi:10.1016/j.placenta.2020.12.003.
[22]	郭书焕, 张青, 马学玲, 等. 妊娠期高血压孕妇血清miR-212-3p和miR-590-3p水平与胎儿生长受限的相关性分析[J]. 中国现代医药杂志, 2023, 25(7):52-56.
	GUO S H, ZHANG Q, MA X L, et al. Correlation analysis of serum miR-212-3p and miR-590-3p levels with fetal growth restriction in pregnant women with gestational hypertension[J]. Chinese Journal of Modern Medicine, 2023, 25(7):52-56. doi:10.3969/j.issn.1672-9463.2023.07.011.

基因名称	引物序列（5′→3′）	产物大小/bp
miR-1227-3p	上游：AGGACGGCTCCTCTAACCAT 下游：AGCGGCTCCACAAGTAAGAC	183
miR-212-3p	上游：AACCAGCGCATGGACAGTTA 下游：GACTTGACCACCGAACCCAT	178
U6	上游：CTCGCTTCGGCAGCACA 下游：ACGCTTCACGAATTTGCG	163

基因名称	引物序列（5′→3′）	产物大小/bp
miR-1227-3p	上游：AGGACGGCTCCTCTAACCAT 下游：AGCGGCTCCACAAGTAAGAC	183
miR-212-3p	上游：AACCAGCGCATGGACAGTTA 下游：GACTTGACCACCGAACCCAT	178
U6	上游：CTCGCTTCGGCAGCACA 下游：ACGCTTCACGAATTTGCG	163

组别	n		年龄/岁		BMI/（kg/m²）		身高/cm	分娩孕周/周
对照组	120		28.67±3.52		27.65±2.19		158.62±2.86	38.58±1.41
研究组	120		28.59±3.48		27.45±2.31		157.96±2.85	38.45±1.52
t或χ²			0.177		0.688		1.791	0.448
组别		分娩方式				孕次/次			产次/次
组别		顺产		剖宫产		孕次/次			产次/次
对照组		68（56.67）		52（43.33）		2.46±0.41			1.58±0.31
研究组		70（58.33）		50（41.67）		2.48±0.43			1.59±0.32
t或χ²		0.068				0.369			0.246

组别	n		年龄/岁		BMI/（kg/m²）		身高/cm	分娩孕周/周
对照组	120		28.67±3.52		27.65±2.19		158.62±2.86	38.58±1.41
研究组	120		28.59±3.48		27.45±2.31		157.96±2.85	38.45±1.52
t或χ²			0.177		0.688		1.791	0.448
组别		分娩方式				孕次/次			产次/次
组别		顺产		剖宫产		孕次/次			产次/次
对照组		68（56.67）		52（43.33）		2.46±0.41			1.58±0.31
研究组		70（58.33）		50（41.67）		2.48±0.43			1.59±0.32
t或χ²		0.068				0.369			0.246

组别	n	血清		胎盘
组别	n	miR-1227-3p	miR-212-3p	miR-1227-3p	miR-212-3p
对照组	120	1.01±0.21	1.01±0.24	1.02±0.30	1.00±0.27
研究组	120	0.54±0.12	1.47±0.25	0.56±0.16	1.56±0.29
t		21.287^＊	14.540^＊	14.821^＊	15.482^＊