miR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin

Abstract

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients’ blood. miR-373-3p was increased in PTL patients’ blood, and was the most expressed in PTL patients’ blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients’ blood, and their expression were the lowest in PTL patients’ blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.

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

“…Besides evidence of increased miR-373-3p levels in multiple cancers [34][35][36][37], research has demonstrated its upregulation in preterm labor placentas relative to normal placentas [13], a finding partially consistent with our observation in the placental tissues of smaller sIUGR fetuses. It is well-known that placentation relies heavily on the proliferative and migratory abilities of trophoblast cells [19]; therefore, any factors that alter these properties affect placental development.…”

“…It is well-known that placentation relies heavily on the proliferative and migratory abilities of trophoblast cells [19]; therefore, any factors that alter these properties affect placental development. The observations by Lee and colleagues, together with our findings of increased expression in placental tissues and a regulatory action on trophoblast cells, robustly support the key role of miR-373-3p in placental development [13]. This further highlights the significance of deregulated miRNAs, such as miR-210, miR-376c, and miR-455 [38][39][40], as well as miR-373-3p validated in this study, in the development of placenta-related disorders.…”

“…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.…”

“…By regulating target genes, miR-373-3p of the miRNA-371-372-373 family has been implicated in the development of multiple cancers [24][25][26][27][28]. Notably, a recent study also described the involvement of miR-373-3p in a pregnancy disorder, showing that it significantly impaired the migratory and invading capability of placental trophoblast cells by targeting CD44 and radixin [13]. The role of miR-373-3p and of its potential target SLC38A1 in the pathogenesis of sIUGR has not yet been explored by bioinformatic analysis.…”

SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway

“…Consistent with the results, early studies have shown the crucial roles of miRNAs in the biological function of trophoblasts. For instance, miR-373-3p has been proved to suppress migration and invasion of trophoblasts by targeting CD44 and Radixin, 31 and Hayder et al. 21 highlighted that miR-210-3p upregulation could damage USAR-related biological functions of extravillous trophoblasts.…”