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MicroRNA-454 contributes to sustaining the proliferation and invasion of trophoblast cells through inhibiting Nodal/ALK7 signaling in pre-eclampsia.
Chem Biol Interact 2019; 298:8-14CB

Abstract

MicroRNAs (miRNAs) are emerging as important regulators in the pathogenesis of pre-eclampsia (PE). Recent evidence has reported that miR-454 plays an important role in regulating cell proliferation and invasion. The decreased proliferation and invasion of trophoblast cells contribute to the pathogenesis of PE. However, whether miR-454 is involved in the regulation of trophoblast cell proliferation and invasion remains unknown. In this study, we aimed to investigate the potential role and underlying mechanism of miR-454 in regulating trophoblast cell proliferation and invasion in vitro. We found that miR-454 expression was significantly decreased in placental tissues from PE patients compared to controls. Transfection of miR-454 mimics promoted the proliferation, reduced the apoptosis, and increased invasion of trophoblast cells, while transfection of miR-454 inhibitor showed opposite effects. Bioinformatics analysis showed that activin receptor-like kinase 7 (ALK7) was a potential target gene of miR-454. Dual-luciferase reporter assay showed miR-454 directly targeted the 3'-untranslated region of AKL7. Further experiments showed that miR-454 negatively regulated ALK7 expression. Interestingly, transfection of miR-454 mimics significantly abrogated the inhibitory effect of Nodal on trophoblast cell proliferation and invasion. Moreover, overexpression of ALK7 markedly reversed the promotion effect of miR-454 on trophoblast cell proliferation and invasion. Overall, our results suggest that miR-454 promotes the proliferation and invasion of trophoblast cells by downregulation of ALK7. Our study suggests that miR-454 may play critical roles in the pathogenesis of PE and serve as a potential therapeutic target for treatment of PE.

Authors+Show Affiliations

Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China.Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China.Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China.Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China.Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China.Department of Obstetrics, Shaanxi Provincial People's Hospital, Xi'an 710068, China. Electronic address: wangyaqin_spph@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30367833

Citation

Shi, Ziyun, et al. "MicroRNA-454 Contributes to Sustaining the Proliferation and Invasion of Trophoblast Cells Through Inhibiting Nodal/ALK7 Signaling in Pre-eclampsia." Chemico-biological Interactions, vol. 298, 2019, pp. 8-14.
Shi Z, She K, Li H, et al. MicroRNA-454 contributes to sustaining the proliferation and invasion of trophoblast cells through inhibiting Nodal/ALK7 signaling in pre-eclampsia. Chem Biol Interact. 2019;298:8-14.
Shi, Z., She, K., Li, H., Yuan, X., Han, X., & Wang, Y. (2019). MicroRNA-454 contributes to sustaining the proliferation and invasion of trophoblast cells through inhibiting Nodal/ALK7 signaling in pre-eclampsia. Chemico-biological Interactions, 298, pp. 8-14. doi:10.1016/j.cbi.2018.10.012.
Shi Z, et al. MicroRNA-454 Contributes to Sustaining the Proliferation and Invasion of Trophoblast Cells Through Inhibiting Nodal/ALK7 Signaling in Pre-eclampsia. Chem Biol Interact. 2019 Jan 25;298:8-14. PubMed PMID: 30367833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-454 contributes to sustaining the proliferation and invasion of trophoblast cells through inhibiting Nodal/ALK7 signaling in pre-eclampsia. AU - Shi,Ziyun, AU - She,Kaie, AU - Li,Hong, AU - Yuan,Xiaohua, AU - Han,Xi, AU - Wang,Yaqin, Y1 - 2018/10/24/ PY - 2018/07/07/received PY - 2018/10/08/revised PY - 2018/10/18/accepted PY - 2018/10/28/pubmed PY - 2019/1/10/medline PY - 2018/10/28/entrez KW - ALK7 KW - Nodal KW - Pre-eclampsia KW - miR-454 SP - 8 EP - 14 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 298 N2 - MicroRNAs (miRNAs) are emerging as important regulators in the pathogenesis of pre-eclampsia (PE). Recent evidence has reported that miR-454 plays an important role in regulating cell proliferation and invasion. The decreased proliferation and invasion of trophoblast cells contribute to the pathogenesis of PE. However, whether miR-454 is involved in the regulation of trophoblast cell proliferation and invasion remains unknown. In this study, we aimed to investigate the potential role and underlying mechanism of miR-454 in regulating trophoblast cell proliferation and invasion in vitro. We found that miR-454 expression was significantly decreased in placental tissues from PE patients compared to controls. Transfection of miR-454 mimics promoted the proliferation, reduced the apoptosis, and increased invasion of trophoblast cells, while transfection of miR-454 inhibitor showed opposite effects. Bioinformatics analysis showed that activin receptor-like kinase 7 (ALK7) was a potential target gene of miR-454. Dual-luciferase reporter assay showed miR-454 directly targeted the 3'-untranslated region of AKL7. Further experiments showed that miR-454 negatively regulated ALK7 expression. Interestingly, transfection of miR-454 mimics significantly abrogated the inhibitory effect of Nodal on trophoblast cell proliferation and invasion. Moreover, overexpression of ALK7 markedly reversed the promotion effect of miR-454 on trophoblast cell proliferation and invasion. Overall, our results suggest that miR-454 promotes the proliferation and invasion of trophoblast cells by downregulation of ALK7. Our study suggests that miR-454 may play critical roles in the pathogenesis of PE and serve as a potential therapeutic target for treatment of PE. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/30367833/MicroRNA_454_contributes_to_sustaining_the_proliferation_and_invasion_of_trophoblast_cells_through_inhibiting_Nodal/ALK7_signaling_in_pre_eclampsia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(18)30890-1 DB - PRIME DP - Unbound Medicine ER -