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MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal.
J Cell Sci 2012; 125(Pt 13):3124-32JC

Abstract

Nodal is a member of the transforming growth factor-β superfamily that plays crucial roles during embryogenesis. Recently, we have reported that Nodal inhibits trophoblast cell proliferation, migration and invasion, but induces apoptosis in the human placenta. In this study, we examined the regulation of Nodal by microRNAs. In silico analysis of Nodal 3'UTR revealed a potential binding site for miR-378a-5p. In luciferase reporter assays, we found that miR-378a-5p suppressed the luciferase activity of a reporter plasmid containing Nodal 3'UTR but this suppressive effect was completely abolished when the predicted target site was mutated. Western blot analysis showed that miR-378a-5p decreased whereas anti-miR-378a-5p increased Nodal protein levels. These results indicate that miR-378a-5p targets Nodal 3'UTR to repress its expression. Stable transfection of the miR-378a-5p precursor, mir-378a, into HTR8/SVneo cells enhanced cell survival, proliferation, migration and invasion. Transient transfection of mature miR-378a-5p mimic, and to a lesser extent, siRNA targeting Nodal, produced similar effects. However, anti-miR-378a-5p inhibited cell migration and invasion. In addition, overexpression of Nodal reversed the invasion-promoting effect of miR-378a-5p. Furthermore, miR-378a-5p enhanced, whereas anti-miR-378a-5p suppressed, the outgrowth and spreading of extravillous trophoblast cells in first trimester placental explants. Finally, miR-378a-5p was detected in human placenta throughout different stages of gestation and in preterm pregnancies, placental miR-378a-5p levels were lower in preeclamptic patients than in healthy controls. Taken together, these findings strongly suggest that miR-378a-5p plays an important role in human placental development by regulating trophoblast cell growth, survival, migration and invasion, and that miR-378a-5p exerts these effects, at least in part, through the suppression of Nodal expression.

Authors+Show Affiliations

Department of Biology, York University, Toronto, ON, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

22454525

Citation

Luo, Linlin, et al. "MicroRNA-378a-5p Promotes Trophoblast Cell Survival, Migration and Invasion By Targeting Nodal." Journal of Cell Science, vol. 125, no. Pt 13, 2012, pp. 3124-32.
Luo L, Ye G, Nadeem L, et al. MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. J Cell Sci. 2012;125(Pt 13):3124-32.
Luo, L., Ye, G., Nadeem, L., Fu, G., Yang, B. B., Honarparvar, E., ... Peng, C. (2012). MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. Journal of Cell Science, 125(Pt 13), pp. 3124-32. doi:10.1242/jcs.096412.
Luo L, et al. MicroRNA-378a-5p Promotes Trophoblast Cell Survival, Migration and Invasion By Targeting Nodal. J Cell Sci. 2012 Jul 1;125(Pt 13):3124-32. PubMed PMID: 22454525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. AU - Luo,Linlin, AU - Ye,Gang, AU - Nadeem,Lubna, AU - Fu,Guodong, AU - Yang,Burton B, AU - Honarparvar,Eilyad, AU - Dunk,Caroline, AU - Lye,Stephen, AU - Peng,Chun, Y1 - 2012/03/27/ PY - 2012/3/29/entrez PY - 2012/3/29/pubmed PY - 2013/1/18/medline SP - 3124 EP - 32 JF - Journal of cell science JO - J. Cell. Sci. VL - 125 IS - Pt 13 N2 - Nodal is a member of the transforming growth factor-β superfamily that plays crucial roles during embryogenesis. Recently, we have reported that Nodal inhibits trophoblast cell proliferation, migration and invasion, but induces apoptosis in the human placenta. In this study, we examined the regulation of Nodal by microRNAs. In silico analysis of Nodal 3'UTR revealed a potential binding site for miR-378a-5p. In luciferase reporter assays, we found that miR-378a-5p suppressed the luciferase activity of a reporter plasmid containing Nodal 3'UTR but this suppressive effect was completely abolished when the predicted target site was mutated. Western blot analysis showed that miR-378a-5p decreased whereas anti-miR-378a-5p increased Nodal protein levels. These results indicate that miR-378a-5p targets Nodal 3'UTR to repress its expression. Stable transfection of the miR-378a-5p precursor, mir-378a, into HTR8/SVneo cells enhanced cell survival, proliferation, migration and invasion. Transient transfection of mature miR-378a-5p mimic, and to a lesser extent, siRNA targeting Nodal, produced similar effects. However, anti-miR-378a-5p inhibited cell migration and invasion. In addition, overexpression of Nodal reversed the invasion-promoting effect of miR-378a-5p. Furthermore, miR-378a-5p enhanced, whereas anti-miR-378a-5p suppressed, the outgrowth and spreading of extravillous trophoblast cells in first trimester placental explants. Finally, miR-378a-5p was detected in human placenta throughout different stages of gestation and in preterm pregnancies, placental miR-378a-5p levels were lower in preeclamptic patients than in healthy controls. Taken together, these findings strongly suggest that miR-378a-5p plays an important role in human placental development by regulating trophoblast cell growth, survival, migration and invasion, and that miR-378a-5p exerts these effects, at least in part, through the suppression of Nodal expression. SN - 1477-9137 UR - https://www.unboundmedicine.com/medline/citation/22454525/MicroRNA_378a_5p_promotes_trophoblast_cell_survival_migration_and_invasion_by_targeting_Nodal_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=22454525 DB - PRIME DP - Unbound Medicine ER -