Format

Send to

Choose Destination
Int J Biochem Cell Biol. 2017 Jun;87:95-103. doi: 10.1016/j.biocel.2017.04.005. Epub 2017 Apr 12.

Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development.

Author information

1
Obstetrical Department, Shaoxing Women and Children's Hospital, Shaoxing, Zhejiang, China.
2
Department of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
3
Genetic Laboratory, Shaoxing Women and Children's Hospital, Shaoxing, Zhejiang, China.
4
Genetic Laboratory, Shaoxing Women and Children's Hospital, Shaoxing, Zhejiang, China. Electronic address: epitach@126.com.

Abstract

Preeclampsia (PE) is a major contributor to maternal morbidity and mortality. However, the molecular mechanisms underlying PE progression are not well characterized. Here, we investigated the role of miR-218 in PE development. The expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in preeclamptic placentae compared to normal placentae. miR-218 expression was induced by hypoxia and decreased after knockdown of HIF-1α in an extravillous trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed direct binding of HIF-1α to the promoters of SLIT2 and SLIT3. Bioinformatics analysis identified LASP1 as a direct target of miR-218. Overexpression of miR-218 repressed the expression of LASP1 at both the mRNA and protein level. Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the 3'-untranslated region of the LASP1 gene. Furthermore, expression of LASP1 rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together, these results indicated that miR-218 contributes to PE by targeting LASP1 to inhibit trophoblast invasion.

KEYWORDS:

Hypoxia; LASP1; Preeclampsia; Trophoblast invasion; miR-218

PMID:
28412444
DOI:
10.1016/j.biocel.2017.04.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center