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MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion.
Hypertension. 2013 Apr; 61(4):864-72.H

Abstract

Preeclampsia is a major disorder of pregnancy and a leading cause of maternal and perinatal morbidity and mortality. MicroRNAs are small noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we examined the expression of miR-376c and found that miR-376c levels were downregulated in both placental and plasma samples collected from preeclamptic patients, when compared with the normal pregnant women at the same gestational stage. Overexpression of miR-376c induced trophoblast cell proliferation, migration, and invasion in HTR8/SVneo cells and promoted placental explant outgrowth. In contrast, inhibition of endogenous miR-376c resulted in a decrease in trophoblast cell invasion and placental explant outgrowth. We identified activin receptor-like kinase 5 (ALK5), a type I receptor for transforming growth factor-β, and ALK7, a type I receptor for Nodal, as targets of miR-376c. Overexpression of miR-376c repressed transforming growth factor-β and Nodal functions, whereas overexpression of ALK5 and ALK7 reversed the effects of miR-376c. These results demonstrate that miR-376c inhibits both ALK5 and ALK7 expression to impair transforming growth factor-β/Nodal signaling, leading to increases in cell proliferation and invasion. An unbalanced Nodal/transforming growth factor-β and miR-376c expression may lead to the development of preeclampsia.

Authors+Show Affiliations

Department of Biology, York University, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23424236

Citation

Fu, Guodong, et al. "MicroRNA-376c Impairs Transforming Growth Factor-β and Nodal Signaling to Promote Trophoblast Cell Proliferation and Invasion." Hypertension (Dallas, Tex. : 1979), vol. 61, no. 4, 2013, pp. 864-72.
Fu G, Ye G, Nadeem L, et al. MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion. Hypertension. 2013;61(4):864-72.
Fu, G., Ye, G., Nadeem, L., Ji, L., Manchanda, T., Wang, Y., Zhao, Y., Qiao, J., Wang, Y. L., Lye, S., Yang, B. B., & Peng, C. (2013). MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion. Hypertension (Dallas, Tex. : 1979), 61(4), 864-72. https://doi.org/10.1161/HYPERTENSIONAHA.111.203489
Fu G, et al. MicroRNA-376c Impairs Transforming Growth Factor-β and Nodal Signaling to Promote Trophoblast Cell Proliferation and Invasion. Hypertension. 2013;61(4):864-72. PubMed PMID: 23424236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion. AU - Fu,Guodong, AU - Ye,Gang, AU - Nadeem,Lubna, AU - Ji,Lei, AU - Manchanda,Tanita, AU - Wang,Yongqing, AU - Zhao,Yangyu, AU - Qiao,Jie, AU - Wang,Yan-Ling, AU - Lye,Stephen, AU - Yang,Burton B, AU - Peng,Chun, Y1 - 2013/02/19/ PY - 2013/2/21/entrez PY - 2013/2/21/pubmed PY - 2013/5/8/medline SP - 864 EP - 72 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 61 IS - 4 N2 - Preeclampsia is a major disorder of pregnancy and a leading cause of maternal and perinatal morbidity and mortality. MicroRNAs are small noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we examined the expression of miR-376c and found that miR-376c levels were downregulated in both placental and plasma samples collected from preeclamptic patients, when compared with the normal pregnant women at the same gestational stage. Overexpression of miR-376c induced trophoblast cell proliferation, migration, and invasion in HTR8/SVneo cells and promoted placental explant outgrowth. In contrast, inhibition of endogenous miR-376c resulted in a decrease in trophoblast cell invasion and placental explant outgrowth. We identified activin receptor-like kinase 5 (ALK5), a type I receptor for transforming growth factor-β, and ALK7, a type I receptor for Nodal, as targets of miR-376c. Overexpression of miR-376c repressed transforming growth factor-β and Nodal functions, whereas overexpression of ALK5 and ALK7 reversed the effects of miR-376c. These results demonstrate that miR-376c inhibits both ALK5 and ALK7 expression to impair transforming growth factor-β/Nodal signaling, leading to increases in cell proliferation and invasion. An unbalanced Nodal/transforming growth factor-β and miR-376c expression may lead to the development of preeclampsia. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/23424236/MicroRNA_376c_impairs_transforming_growth_factor_β_and_nodal_signaling_to_promote_trophoblast_cell_proliferation_and_invasion_ L2 - http://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.111.203489?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -