Long non‑coding RNA NR_002794 is upregulated in pre‑eclampsia and regulates the proliferation, apoptosis and invasion of trophoblast cells

Ma,Yinyao; Liang,Xuxia; Wu,Hua; Zhang,Chun; Ma,Yanhua

doi:10.3892/mmr.2019.10701

Long non‑coding RNA NR_002794 is upregulated in pre‑eclampsia and regulates the proliferation, apoptosis and invasion of trophoblast cells

Authors:
- Yinyao Ma
- Xuxia Liang
- Hua Wu
- Chun Zhang
- Yanhua Ma
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Affiliations: Department of Obstetrics, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
Published online on: September 24, 2019 https://doi.org/10.3892/mmr.2019.10701
Pages: 4567-4575
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pre‑eclampsia is a common complication during pregnancy, characterized by hypertension and proteinuria. The pathogenesis of pre‑eclampsia is not fully understood. Studies on the maternal spiral artery have led scientists to consider that the ineffective infiltration of placental trophoblast cells may be a primary cause of pre‑eclampsia. The present study aimed to investigate the differences in the profiles of long non‑coding RNAs (lncRNAs) between the placentas of patients with pre‑eclampsia and those of healthy pregnant women. The involvement of the differentially expressed lncRNAs in the biological activity of trophoblast cells was also assessed. A total of 26 differentially expressed lncRNAs were identified between the pre‑eclampsia and healthy groups. Upregulation of NR_002794 was found in tissues from patients with pre‑eclampsia. In SWAN71 trophoblast cells, NR_002794 had suppressive effects on proliferation and migration, and resulted in an increased rate of apoptosis. Furthermore, lncRNA NR_002794 had no effect on the phagocytosis of trophoblast cells. The present study suggested that abnormal levels of NR_002794 may lead to atypical conditions in trophoblast cells, which may be associated with the failure of maternal spiral artery remodeling during pregnancy and, consequently, with the development of pre‑eclampsia.

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1	Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM and Hofmeyr GJ: Pre-eclampsia. Lancet. 387:999–1011. 2016. View Article : Google Scholar : PubMed/NCBI
2	Ahn S, Jeong E, Min JW, Kim E, Choi SS, Kim CJ and Lee DC: Identification of genes dysregulated by elevation of microRNA-210 levels in human trophoblasts cell line, Swan 71. Am J Reprod Immunol. 78:e127222017. View Article : Google Scholar
3	Souza JP, Gulmezoglu AM, Vogel J, Carroli G, Lumbiganon P, Qureshi Z, Costa MJ, Fawole B, Mugerwa Y, Nafiou I, et al: Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): A cross-sectional study. Lancet. 381:1747–1755. 2013. View Article : Google Scholar : PubMed/NCBI
4	Hansen AR, Barnes CM, Folkman J and McElrath TF: Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr. 156:532–536. 2010. View Article : Google Scholar : PubMed/NCBI
5	Strand KM, Heimstad R, Iversen AC, Austgulen R, Lydersen S, Andersen GL, Irgens LM and Vik T: Mediators of the association between pre-eclampsia and cerebral palsy: Population based cohort study. BMJ. 347:f40892013. View Article : Google Scholar : PubMed/NCBI
6	Irgens HU, Reisaeter L, Irgens LM and Lie RT: Long term mortality of mothers and fathers after pre-eclampsia: Population based cohort study. BMJ. 323:1213–1217. 2001. View Article : Google Scholar : PubMed/NCBI
7	Huppertz B: Placental origins of preeclampsia: Challenging the current hypothesis. Hypertension. 51:970–975. 2008. View Article : Google Scholar : PubMed/NCBI
8	Du MR, Wang SC and Li DJ: The integrative roles of chemokines at the maternal-fetal interface in early pregnancy. Cell Mol Immunol. 11:438–448. 2014. View Article : Google Scholar : PubMed/NCBI
9	Liu X, Chen H, Kong W, Zhang Y, Cao L, Gao L and Zhou R: Down-regulated long non-coding RNA-ATB in preeclampsia and its effect on suppressing migration, proliferation, and tube formation of trophoblast cells. Placenta. 49:80–87. 2017. View Article : Google Scholar : PubMed/NCBI
10	Chakraborty C, Gleeson LM, McKinnon T and Lala PK: Regulation of human trophoblast migration and invasiveness. Can J Physiol Pharmacol. 80:116–124. 2002. View Article : Google Scholar : PubMed/NCBI
11	Zou Y, Jiang Z, Yu X, Sun M, Zhang Y, Zuo Q, Zhou J, Yang N, Han P, Ge Z, et al: Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. PLoS One. 8:e795982013. View Article : Google Scholar : PubMed/NCBI
12	Zhang Y, Zou Y, Wang W, Zuo Q, Jiang Z, Sun M, De W and Sun L: Down-regulated long non-coding RNA MEG3 and its effect on promoting apoptosis and suppressing migration of trophoblast cells. J Cell Biochem. 116:542–550. 2015. View Article : Google Scholar : PubMed/NCBI
13	Akhade VS, Pal D and Kanduri C: Long noncoding RNA: Genome organization and mechanism of action. Adv Exp Med Biol. 1008:47–74. 2017. View Article : Google Scholar : PubMed/NCBI
14	Guo X and Hua Y: CCAT1: An oncogenic long noncoding RNA in human cancers. J Cancer Res Clin Oncol. 143:555–562. 2017. View Article : Google Scholar : PubMed/NCBI
15	Johnson R: Long non-coding RNAs in Huntington's disease neurodegeneration. Neurobiol Dis. 46:245–254. 2012. View Article : Google Scholar : PubMed/NCBI
16	He X, He Y, Xi B, Zheng J, Zeng X, Cai Q, Ouyang Y, Wang C, Zhou X, Huang H, et al: LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis. PLoS One. 8:e814372013. View Article : Google Scholar : PubMed/NCBI
17	Chen H, Meng T, Liu X, Sun M, Tong C, Liu J, Wang H and Du J: Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. Int J Clin Exp Pathol. 8:12718–12727. 2015.PubMed/NCBI
18	Zou YF and Sun LZ: Long noncoding RNA HOTAIR modulates the function of trophoblast cells in pre-eclampsia. Sichuan Da Xue Xue Bao Yi Xue Ban. 46113–117. (122)2015.(In Chinese). PubMed/NCBI
19	Gao C, Zhao D, Zhao Q, Dong D, Mu L, Zhao X, Guo M, Xu A, Fang L, Liu Q and Che J: Microarray profiling and co-expression network analysis of lncRNAs and mRNAs in ovarian cancer. Cell Death Discov. 5:932019. View Article : Google Scholar : PubMed/NCBI
20	Mlecnik B, Galon J and Bindea G: Comprehensive functional analysis of large lists of genes and proteins. J Proteomics. 171:2–10. 2018. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Ray JG, Vermeulen MJ, Schull MJ and Redelmeier DA: Cardiovascular health after maternal placental syndromes (CHAMPS): Population-based retrospective cohort study. Lancet. 366:1797–1803. 2005. View Article : Google Scholar : PubMed/NCBI
23	ACOG Committee on Practice Bulletins-Obstetrics, . ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. 99:159–167. 2002.PubMed/NCBI
24	Álvarez-Cabrera MC, Barrientos-Galeana E, Barrera-García A, Osorio-Caballero M, Acevedo JF, Flores-Herrera O, Díaz NF, Molina-Hernández A, García-López G and Flores-Herrera H: Secretion of heat shock −60, −70 kD protein, IL-1β and TNFα levels in serum of a term normal pregnancy and patients with pre-eclampsia development. J Cell Mol Med. 22:5748–5752. 2018. View Article : Google Scholar : PubMed/NCBI
25	Schlichting LE, Insaf TZ, Zaidi AN, Lui GK and Van Zutphen AR: Maternal comorbidities and complications of delivery in pregnant women with congenital heart disease. J Am Coll Cardiol. 73:2181–2191. 2019. View Article : Google Scholar : PubMed/NCBI
26	Heazell AE, Buttle HR, Baker PN and Crocker IP: Altered expression of regulators of caspase activity within trophoblast of normal pregnancies and pregnancies complicated by preeclampsia. Reprod Sci. 15:1034–1043. 2008. View Article : Google Scholar : PubMed/NCBI
27	Gloss BS and Dinger ME: The specificity of long noncoding RNA expression. Biochim Biophys Acta. 1859:16–22. 2016. View Article : Google Scholar : PubMed/NCBI
28	Shi Q and Yang X: Circulating MicroRNA and long noncoding RNA as biomarkers of cardiovascular diseases. J Cell Physiol. 231:751–755. 2016. View Article : Google Scholar : PubMed/NCBI
29	Zhang Z, Tang J, Di R, Liu Q, Wang X, Gan S, Zhang X, Zhang J, Hu W and Chu M: Comparative transcriptomics reveal key sheep (Ovis aries) hypothalamus LncRNAs that affect reproduction. Animals (Basel). 9(pii): E1522019. View Article : Google Scholar : PubMed/NCBI
30	Sun W, Yang Y, Xu C and Guo J: Regulatory mechanisms of long noncoding RNAs on gene expression in cancers. Cancer Genet. 216-217:105–110. 2017. View Article : Google Scholar : PubMed/NCBI
31	Pengjie Z, Xionghui C, Yueming Z, Ting X, Na L, Jianying T and Zhice X: LncRNA uc003fir promotes CCL5 expression and negatively affects proliferation and migration of trophoblast cells in preeclampsia. Pregnancy Hypertens. 14:90–96. 2018. View Article : Google Scholar : PubMed/NCBI
32	Yang Y, Xi L, Ma Y, Zhu X, Chen R, Luan L, Yan J and An R: The lncRNA small nucleolar RNA host gene 5 regulates trophoblast cell proliferation, invasion, and migration via modulating miR-26a-5p/N-cadherin axis. J Cell Biochem. 120:3173–3184. 2019. View Article : Google Scholar : PubMed/NCBI