MicroRNA‑144‑3p may participate in the pathogenesis of preeclampsia by targeting Cox‑2

Hu,Suwei; Li,Jie; Tong,Ming; Li,Qian; Chen,Yong; Lu,Hongmei; Wang,Yixiong; Min,Lingfeng

doi:10.3892/mmr.2019.10150

MicroRNA‑144‑3p may participate in the pathogenesis of preeclampsia by targeting Cox‑2

Authors:
- Suwei Hu
- Jie Li
- Ming Tong
- Qian Li
- Yong Chen
- Hongmei Lu
- Yixiong Wang
- Lingfeng Min
View Affiliations

Affiliations: Department of Gynaecology and Obstetrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Medical Genetic Center, The Affiliated Hospital of Yangzhou University, Yangzhou Women and Children Hospital, Yangzhou, Jiangsu 225002, P.R. China, Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, P.R. China
Published online on: April 11, 2019 https://doi.org/10.3892/mmr.2019.10150
Pages: 4655-4662
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Preeclampsia remains a major cause of maternal mortality and morbidity worldwide. It is generally accepted that the development of the placenta, including spiral artery remodelling, normal trophoblast cells function and maternal‑fetal inflammation‑immune interactions, is critical for the pathogenesis of preeclampsia. Several investigations have demonstrated that microRNAs (miRNAs/miRs) in the placenta may be potential molecular markers for diagnosis of preeclampsia. In the current study, the aim was to investigate the expression of miR‑144‑3p in the placenta of patients with preeclampsia and normal placentas, and to explore the potential target genes. miRNA microarray analysis was performed using three paired placentas (preeclampsia and normal) in order to find differential expression of miRNAs. Following this, miR‑144‑3p was selected as a differentially expressed miRNA and validated using in situ hybridization to determine the clinical significance in placentas with preeclampsia. A potential target gene of miR‑144‑3p, cyclooxygenase‑2 (Cox‑2), was identified by bioinformatics, luciferase reporter assay and western blotting. The expression of Cox‑2 was also examined by immunohistochemical staining of samples of placenta from patients with preeclampsia and normal placenta. Western blot analysis was performed to investigate the effect of miR‑144‑3p on the expression of Cox‑2 in HTR‑8/SVneo cells in vitro. miR‑144‑3p was decreased in placentas from patients with preeclampsia. A luciferase reporter assay demonstrated that Cox‑2 was a potential miR‑144‑3p target gene and the result was verified by western blotting. A negative correlation was observed between miR‑144‑3p and Cox‑2 in preeclamptic placenta by immunohistochemical staining and in situ hybridization. Western blot analysis demonstrated that overexpression of miR‑144‑3p decreased Cox‑2 expression by 38.2% in HTR‑8/SVneo cells. Understanding the differential expression of miR‑144‑3p and its association with Cox‑2 may aid the exploration of the pathogenesis of preeclampsia, and contribute to the development of miRNA‑based therapies in the future.

View Figures

View References

1	Kanasaki K and Kalluri R: The biology of preeclampsia. Kidney Int. 76:831–837. 2009. View Article : Google Scholar : PubMed/NCBI
2	Redman CW and Sargent IL: Latest advances in understanding preeclampsia. Science. 308:1592–1594. 2005. View Article : Google Scholar : PubMed/NCBI
3	Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot C and Hofmeyr GJ: Pre-eclampsia. Lancet. 387:999–1011. 2016. View Article : Google Scholar : PubMed/NCBI
4	Phipps E, Prasanna D, Brima W and Jim B: Preeclampsia: Updates in pathogenesis, definitions, and guidelines. Clin J Am Soc Nephrol. 11:1102–1113. 2016. View Article : Google Scholar : PubMed/NCBI
5	Roberts JM and Cooper DW: Pathogenesis and genetics of pre-eclampsia. Lancet. 357:53–56. 2001. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Zhang C: MicroRNomics: A newly emerging approach for disease biology. Physiol Genomics. 33:139–147. 2008. View Article : Google Scholar : PubMed/NCBI
8	Pineles BL, Romero R, Montenegro D, Tarca AL, Han YM, Kim YM, Draghici S, Espinoza J, Kusanovic JP, Mittal P, et al: Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol. 196:261.e1–e6. 2007. View Article : Google Scholar
9	Hu Y, Li P, Hao S, Liu L, Zhao J and Hou Y: Differential expression of microRNAs in the placentae of Chinese patients with severe pre-eclampsia. Clin Chem Lab Med. 47:923–929. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhu XM, Han T, Sargent IL, Yin GW and Yao YQ: Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol. 200:661.e1–e7. 2009. View Article : Google Scholar
11	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 42015.doi: 10.7554/eLife.05005.
12	Xiao J, Tao T, Yin Y, Zhao L, Yang L and Hu L: miR-144 may regulate the proliferation, migration and invasion of trophoblastic cells through targeting PTEN in preeclampsia. Biomed Pharmacother. 94:341–353. 2017. View Article : Google Scholar : PubMed/NCBI
13	Choi SY, Yun J, Lee OJ, Han HS, Yeo MK, Lee MA and Suh KS: MicroRNA expression profiles in placenta with severe preeclampsia using a PNA-based microarray. Placenta. 34:799–804. 2013. View Article : Google Scholar : PubMed/NCBI
14	Wu L, Song WY, Xie Y, Hu LL, Hou XM, Wang R, Gao Y, Zhang JN, Zhang L, Li WW, et al: miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly targeting IGF2BP2. Cell Death Dis. 9:162018. View Article : Google Scholar : PubMed/NCBI
15	Gao Y, She R, Wang Q, Li Y and Zhang H: Up-regulation of miR-299 suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting HDAC2 in pre-eclampsia. Biomed Pharmacother. 97:1222–1228. 2018. View Article : Google Scholar : PubMed/NCBI
16	Niu ZR, Han T, Sun XL, Luan LX, Gou WL and Zhu XM: MicroRNA-30a-3p is overexpressed in the placentas of patients with preeclampsia and affects trophoblast invasion and apoptosis by its effects on IGF-1. Am J Obstet Gynecol. 218:249.e1–249.e12. 2018. View Article : Google Scholar
17	Zhang Y, Diao Z, Su L, Sun H, Li R, Cui H and Hu Y: MicroRNA-155 contributes to preeclampsia by down-regulating CYR61. Am J Obstet Gynecol. 202:466.e1–e7. 2010. View Article : Google Scholar
18	Zhao Y, Xie Z, Lin J and Liu P: MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met. Am J Transl Res. 9:2437–2446. 2017.PubMed/NCBI
19	Xiao R, Li C and Chai B: miRNA-144 suppresses proliferation and migration of colorectal cancer cells through GSPT1. Biomed Pharmacother. 74:138–144. 2015. View Article : Google Scholar : PubMed/NCBI
20	Wu M, Huang C, Huang X, Liang R, Feng Y and Luo X: MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma. Oncol Rep. 38:2173–2181. 2017. View Article : Google Scholar : PubMed/NCBI
21	Li RD, Shen CH, Tao YF, Zhang XF, Zhang QB, Ma ZY and Wang ZX: MicroRNA-144 suppresses the expression of cytokines through targeting RANKL in the matured immune cells. Cytokine. 108:197–204. 2018. View Article : Google Scholar : PubMed/NCBI
22	Han S, Zhu J and Zhang Y: miR-144 potentially suppresses proliferation and migration of ovarian cancer cells by targeting RUNX1. Med Sci Monit Basic Res. 24:40–46. 2018. View Article : Google Scholar : PubMed/NCBI
23	Yao Q, Gu A, Wang Z and Xue Y: MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2. Exp Ther Med. 15:3088–3095. 2018.PubMed/NCBI
24	Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB and Lipsky PE: Cyclooxygenase in biology and disease. FASEB J. 12:1063–1073. 1998. View Article : Google Scholar : PubMed/NCBI
25	Bachawaty T, Washington SL and Walsh SW: Neutrophil expression of cyclooxygenase 2 in preeclampsia. Reprod Sci. 17:465–470. 2010. View Article : Google Scholar : PubMed/NCBI
26	Goksu Erol AY, Nazli M and Yildiz SE: Expression levels of cyclooxygenase-2, tumor necrosis factor-alpha and inducible NO synthase in placental tissue of normal and preeclamptic pregnancies. J Matern Fetal Neonatal Med. 25:826–830. 2012. View Article : Google Scholar : PubMed/NCBI
27	Afroze SH, Kalagiri RR, Reyes M, Zimmerman JD, Beeram MR, Drever N, Zawieja DC, Kuehl TJ and Uddin MN: Apoptotic and stress signaling markers are augmented in preeclamptic placenta and umbilical cord. BBA Clin. 6:25–30. 2016. View Article : Google Scholar : PubMed/NCBI
28	Redman CW, Sacks GP and Sargent IL: Preeclampsia: An excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 180:499–506. 1999. View Article : Google Scholar : PubMed/NCBI
29	Sibai B, Dekker G and Kupferminc M: Pre-eclampsia. Lancet. 365:785–799. 2005. View Article : Google Scholar : PubMed/NCBI
30	Akarasereenont P, Techatraisak K, Chotewuttakorn S and Thaworn A: The expression of cyclooxygenase-2 in human umbilical vein endothelial cell culture from preeclampsia. J Med Assoc Thai. 82:167–172. 1999.PubMed/NCBI
31	Wetzka B, Nusing R, Charnock-Jones DS, Schäfer W, Zahradnik HP and Smith SK: Cyclooxygenase-1 and −2 in human placenta and placental bed after normal and pre-eclamptic pregnancies. Hum Reprod. 12:2313–2320. 1997. View Article : Google Scholar : PubMed/NCBI
32	Shah TJ and Walsh SW: Activation of NF-kappaB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia. Am J Obstet Gynecol. 196:48.e1–e8. 2007. View Article : Google Scholar