Expression and role of miR‑338‑3p in peripheral blood and placenta of patients with pregnancy‑induced hypertension

Li,Jun; Wu,Yan; Liu,Hui

doi:10.3892/etm.2020.8719

Expression and role of miR‑338‑3p in peripheral blood and placenta of patients with pregnancy‑induced hypertension

Authors:
- Jun Li
- Yan Wu
- Hui Liu
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Affiliations: Fetal Heart Monitoring Unit, Laiwu Maternal and Child Health Hospital, Laiwu, Shandong 271100, P.R. China, The Fifth Department of Obstetrics and Gynecology, Laiwu Maternal and Child Health Hospital, Laiwu, Shandong 271100, P.R. China
Published online on: May 6, 2020 https://doi.org/10.3892/etm.2020.8719
Pages: 418-426
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role of miR-338-3p in pregnancy-induced hypertension (PIH), and its effects on human trophoblast cells in vitro. Quantitative real‑time PCR was used to detect miR‑338‑3p expression. Human trophoblast HTR8/SVneo cells were transfected with miR‑338‑3p mimics. Effects of miR‑338‑3p on cell proliferation, invasion and metastasis, and anoikis resistance were detected by CCK‑8 assay, Transwell chamber assay, flow cytometry and western blot analysis, respectively. Bioinformatics analysis was performed to predict the target of miR‑338‑3p, and the results were confirmed by dual luciferase reporter assay. The expression level of miR‑338‑3p was significantly upregulated in the peripheral blood and placenta of PIH patients. CCK‑8 assay showed that miR‑338‑3p mimics inhibited the proliferation of HTR8/SVneo cells at indicated time points. Flow cytometry showed that miR‑338‑3p transfection significantly increased the Ki‑67 expression in the HTR8/SVneo cells, indicating enhanced cell proliferation. Transwell chamber assay and western blot analysis showed that the invasion and metastatic abilities of the HTR8/SVneo cells were significantly decreased in the miR‑338‑3p transfection group, as well as expression levels of MMP‑2 and MMP‑9. Bioinformatics analysis and dual luciferase reporter assay indicated that AKT3 is a target gene of miR‑338‑3p. Our results suggest that miR‑338‑3p is significantly increased in the peripheral blood and placenta of PIH patients, which is correlated with the disease development. miR‑338‑3p inhibits proliferation, invasion and metastasis, and apoptosis resistance of human trophoblast cells by targeting AKT3.

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1	Arendt LH, Henriksen TB, Lindhard MS, Parner ET, Olsen J and Ramlau-Hansen CH: Hypertensive disorders of pregnancy and genital anomalies in boys: A Danish Nationwide Cohort Study. Epidemiology. 29:739–748. 2018.PubMed/NCBI View Article : Google Scholar
2	Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G and Ishaku S: International society for the study of hypertension in pregnancy (ISSHP): Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 72:24–43. 2018.PubMed/NCBI View Article : Google Scholar
3	West J, Lawlor DA, Santorelli G, Collings P, Whincup PH, Sattar NA, Farrar D and Wright J: Associations of social and economic and pregnancy exposures with blood pressure in UK White British and Pakistani children age 4/5. Sci Rep. 8(8966)2018.PubMed/NCBI View Article : Google Scholar
4	Li L, Zhao K, Hua J and Li S: Association between sleep-disordered breathing during pregnancy and maternal and fetal outcomes: An updated systematic review and meta-analysis. Front Neurol. 9(91)2018.PubMed/NCBI View Article : Google Scholar
5	Hill W, Holy R and Traiger G: EXPRESS: Intimacy, contraception, and pregnancy prevention in patients with pulmonary arterial hypertension: Are we counseling our patients? Pulm Circ: Jun 12, 2018 (Epub ahead of print).
6	Calimag-Loyola APP and Lerma EV: Renal complications during pregnancy: In the hypertension spectrum. Dis Mon. 65:25–44. 2019.PubMed/NCBI View Article : Google Scholar
7	Hu J, Wang H, Hu YF, Xu XF, Chen YH, Xia MZ, Zhang C and Xu DX: Cadmium induces inflammatory cytokines through activating Akt signaling in mouse placenta and human trophoblast cells. Placenta. 65:7–14. 2018.PubMed/NCBI View Article : Google Scholar
8	Wang H, Wang T, Dai L, Cao W, Ye L, Gao L, Zhou B and Zhou R: Effects of CXCL3 on migration, invasion, proliferation and tube formation of trophoblast cells. Placenta. 66:47–56. 2018.PubMed/NCBI View Article : Google Scholar
9	Zhao HJ, Chang HM, Zhu H, Klausen C, Li Y and Leung PCK: Bone morphogenetic protein 2 promotes human trophoblast cell invasion by inducing activin A production. Endocrinology. 159:2815–2825. 2018.PubMed/NCBI View Article : Google Scholar
10	Huang DJ, Huang ZM, Xiao HY, Wu ZK, Tang LJ and Jiang JH: Protein scaffolded DNA tetrads enable efficient delivery and ultrasensitive imaging of miRNA through crosslinking hybridization chain reaction. Chem Sci. 9:4892–4897. 2018.PubMed/NCBI View Article : Google Scholar
11	Tang J, Zhang Z, Jin X and Shi H: miR-383 negatively regulates osteoblastic differentiation of bone marrow mesenchymal stem cells in rats by targeting Satb2. Bone. 114:137–143. 2018.PubMed/NCBI View Article : Google Scholar
12	Biró O, Alasztics B, Molvarec A, Joó J, Nagy B and Rigó J Jr: Various levels of circulating exosomal total-miRNA and miR-210 hypoxamiR in different forms of pregnancy hypertension. Pregnancy Hypertens. 10:207–212. 2017.PubMed/NCBI View Article : Google Scholar
13	Mei Z, Huang B, Mo Y and Fan J: An exploratory study into the role of miR-204-5p in pregnancy-induced hypertension. Exp Ther Med. 13:1711–1718. 2017.PubMed/NCBI View Article : Google Scholar
14	Wang N, Feng Y, Xu J, Zou J, Chen M, He Y, Liu H, Xue M and Gu Y: miR-362-3p regulates cell proliferation, migration and invasion of trophoblastic cells under hypoxia through targeting Pax3. Biomed Pharmacother. 99:462–468. 2018.PubMed/NCBI View Article : Google Scholar
15	Sun F, Yu M, Yu J, Liu Z, Zhou X, Liu Y, Ge X, Gao H, Li M, Jiang X, et al: miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis. 9(522)2018.PubMed/NCBI View Article : Google Scholar
16	Hua FF, Liu SS, Zhu LH, Wang YH, Liang X, Ma N and Shi HR: MiRNA-338-3p regulates cervical cancer cells proliferation by targeting MACC1 through MAPK signaling pathway. Eur Rev Med Pharmacol Sci. 21:5342–5352. 2017.PubMed/NCBI View Article : Google Scholar
17	Xiao G, Wang Q, Li B, Wu X, Liao H, Ren Y and Ai N: MicroRNA-338-3p suppresses proliferation of human liver cancer cells by targeting SphK2. Oncol Res. 26:1183–1189. 2018.PubMed/NCBI View Article : Google Scholar
18	Che G, Wang Y, Zhou B, Gao L, Wang T, Yuan F and Zhang L: Knockdown of heparanase suppresses invasion of human trophoblasts by activating p38 MAPK signaling pathway. Dis Markers. 2018(7413027)2018.PubMed/NCBI View Article : Google Scholar
19	Li X, Wu C, Shen Y, Wang K, Tang L, Zhou M, Yang M, Pan T, Liu X and Xu W: Ten-eleven translocation 2 demethylates the MMP9 promoter, and its down-regulation in preeclampsia impairs trophoblast migration and invasion. J Biol Chem. 293:10059–10070. 2018.PubMed/NCBI View Article : Google Scholar
20	Monteiro LJ, Cubillos S, Sanchez M, Acuña-Gallardo S, Venegas P, Herrera V, Lam EW, Varas-Godoy M and Illanes SE: Reduced FOXM1 expression limits trophoblast migration and angiogenesis and is associated with preeclampsia. Reprod Sci. 26:580–590. 2019.PubMed/NCBI View Article : Google Scholar
21	Tateishi A, Ohira S, Yamamoto Y and Kanno H: Histopathological findings of pregnancy-induced hypertension: Histopathology of early-onset type reflects two-stage disorder theory. Virchows Arch. 472:635–642. 2018.PubMed/NCBI View Article : Google Scholar
22	Burton GJ and Jauniaux E: Development of the human placenta and fetal heart: Synergic or independent? Front Physiol. 9(373)2018.PubMed/NCBI View Article : Google Scholar
23	Velicky P, Windsperger K, Petroczi K, Pils S, Reiter B, Weiss T, Vondra S, Ristl R, Dekan S, Fiala C, et al: Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia. Sci Rep. 8(6342)2018.PubMed/NCBI View Article : Google Scholar
24	Gao X, Li H and Wei JX: MiR-4421 regulates the progression of preeclampsia by regulating CYP11B2. Eur Rev Med Pharmacol Sci. 22:1533–1540. 2018.PubMed/NCBI View Article : Google Scholar
25	Qin Q, Wei F, Zhang J and Li B: miR-134 suppresses the migration and invasion of non-small cell lung cancer by targeting ITGB1. Oncol Rep. 37:823–830. 2017.PubMed/NCBI View Article : Google Scholar
26	Zhang X, Wang C, Li H, Niu X, Liu X, Pei D, Guo X, Xu X and Li Y: miR-338-3p inhibits the invasion of renal cell carcinoma by downregulation of ALK5. Oncotarget. 8:64106–64113. 2017.PubMed/NCBI View Article : Google Scholar
27	Wu Y, Wang M, Zhang K, Li Y, Xu M, Tang S, Qu X and Li C: Lactate enhanced the effect of parathyroid hormone on osteoblast differentiation via GPR81-PKC-Akt signaling. Biochem Biophys Res Commun. 503:737–743. 2018.PubMed/NCBI View Article : Google Scholar
28	Li Y, Gong Q, Guo W, Kan X, Xu D, Ma H, Fu S and Liu J: Farrerol relieve lipopolysaccharide (LPS)-induced mastitis by inhibiting AKT/NF-κB p65, ERK1/2 and P38 signaling pathway. Int J Mol Sci. 19: pii(E1770)2018.PubMed/NCBI View Article : Google Scholar
29	Justin-Thenmozhi A, Dhivya Bharathi M, Kiruthika R, Manivasagam T, Borah A and Essa MM: Attenuation of aluminum chloride-induced neuroinflammation and caspase activation through the AKT/GSK-3β pathway by hesperidin in Wistar rats. Neurotox Res. 34:463–476. 2018.PubMed/NCBI View Article : Google Scholar
30	Wu X, Gowda NM, Kawasawa YI and Gowda DC: A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-κB signaling independent of MyD88/TRIF and promotes Th2 response. J Biol Chem. 293:10425–10434. 2018.PubMed/NCBI View Article : Google Scholar
31	Wang L, Huang D, Jiang Z, Luo Y, Norris C, Zhang M, Tian X and Tang Y: Akt3 is responsible for the survival and proliferation of embryonic stem cells. Biol Open. 6:850–861. 2017.PubMed/NCBI View Article : Google Scholar
32	Zboray K, Mohrherr J, Stiedl P, Pranz K, Wandruszka L, Grabner B, Eferl R, Moriggl R, Stoiber D, Sakamoto K, et al: AKT3 drives adenoid cystic carcinoma development in salivary glands. Cancer Med. 7:445–453. 2018.PubMed/NCBI View Article : Google Scholar
33	Shi J, Jiang K and Li Z: MiR-145 ameliorates neuropathic pain via inhibiting inflammatory responses and mTOR signaling pathway by targeting Akt3 in a rat model. Neurosci Res. 134:10–17. 2018.PubMed/NCBI View Article : Google Scholar
34	Hu X, Wang J, He W, Zhao P and Ye C: MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer. Oncol Lett. 15:3998–4004. 2018.PubMed/NCBI View Article : Google Scholar