miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction

Abstract

Selective intrauterine growth restriction (sIUGR) is a disorder of monochorionic (MC) twin pregnancies. However, the underlying mechanism remains largely unknown. Trophoblast cells are the major component of the placenta. Dysfunction of trophoblast cells is associated with placental dysfunction. Our previous study identified miR-338-5p is downregulated in placenta tissues sharing larger twins of sIUGR. In the present study, we aimed to investigate the role of miR-338-5p in trophoblast cells and explored its target. Our results further indicated that miR-338-5p was downregulated in placental tissues supporting larger twins of sIUGR, whereas epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was upregulated. Moreover, miR-338-5p overexpression suppressed the growth and invasion of trophoblast cells. Importantly, results from luciferase reporter assay demonstrated that miR-338-5p bound on the 3′-UTR of EFEMP1. miR-338-5p suppressed the growth and invasion of trophoblast cells via targeting EFEMP1. Further, miR-338-5p/EFEMP1 might disrupt the function of trophoblast cells via inhibiting the phosphorylation of AKT.

MiR-338-5p Inhibits EGF-Induced EMT in Pancreatic Cancer Cells by Targeting EGFR/ERK Signaling

“…Activation of the EGFR kinase stimulates the following two signaling pathways: Ras/Raf/MEK/ERK and PI3K/Akt/mTOR ( 25 ). According to recent report, miR-338-5p inhibited the growth and invasion of trophoblast cells by targeting EFEMP1/Akt ( 26 ). However, in current study of PC Capan-2 and PANC-1 cells, we did not find the regulatory effect of miR-338-5p on the expression of p-Akt (S473) and mTOR protein.…”

miR-373-3p Regulates the Proliferative and Migratory Properties of Human HTR8 Cells via SLC38A1 Modulation

“…Selective intrauterine growth restriction (sIUGR) occurs in approximately 10%-15% of monochorionic twins and frequently causes perinatal morbidity and mortality [1,2]. The mechanisms underlying this disorder remain unclear because monochorionic twins originate from the same zygote and have identical genomes [3,4]. Considering the contribution of unequal placental sharing and vascular anastomoses to inconsistent fetal development [4][5][6], it is reasonable to speculate that the pathogenesis may be associated with the transportation of nutrients like amino acids.…”

“…The identical genomes of monochorionic twins have tended to preclude a major influence of genetic information on sIUGR progression, although this does hint at the potential significant roles of epigenetic factors. MicroRNAs (miR-NAs) are short 21-25 nucleotide noncoding RNA molecules that regulate many cellular processes by causing gene-level alterations on binding to the 3 ′ -untranslated region (3 ′ -UTR) of a target gene [3,11]. A growing body of evidence supports the use of miRNAs as potential biomarkers for pregnancy-associated disorders [12][13][14][15][16], with different or abnormal miR-210-3p and miR-338-5p expressions already linked to placental dysfunction in sIUGR [3,[17][18][19].…”

“…MicroRNAs (miR-NAs) are short 21-25 nucleotide noncoding RNA molecules that regulate many cellular processes by causing gene-level alterations on binding to the 3 ′ -untranslated region (3 ′ -UTR) of a target gene [3,11]. A growing body of evidence supports the use of miRNAs as potential biomarkers for pregnancy-associated disorders [12][13][14][15][16], with different or abnormal miR-210-3p and miR-338-5p expressions already linked to placental dysfunction in sIUGR [3,[17][18][19]. Whether other miRNAs have cognate roles in the pathogenesis of sIUGR requires further exploration.…”