Down-regulation of MYO1A inhibits trophoblast cell proliferation and migration through SMURF2/Hedgehog signaling pathway and leads to fetal growth restriction

Introduction

Fetal growth restriction (FGR) is most commonly related to insufficient placental perfusion caused by insufficient trophoblast proliferation and migration. Myosin Ia, encoded by the gene MYO1A, plays an important role in cytoskeleton recombination and cell movement. In this study, we found that downregulation of MYO1A inhibits Hedgehog (Hh) signaling by interacting with SMURF2 in choriocarcinoma cells, leading to FGR.

Methods

A total of 59 placenta samples (26 FGR placentas and 33 normal placentas) were collected. The expression of MYO1A in placental tissues of the two groups was detected by qRT-PCR and Western blotting. The proliferation ability of choriocarcinoma cell lines HTR-8/SVneo and JEG3 was tested by CCK8 and colony formation experiments, and the migration ability was tested by transwell and wound healing experiments. Co-immunoprecipitation assay is used to verify the interaction between myosin Ia and SMURF2.

Result

We found that MYO1A expression was significantly lower in the placentas of pregnant women with FGR than in normal pregnant women. Moreover, the knockdown of MYO1A has been observed to inhibit choriocarcinoma cells proliferation and migration. Downregulation of MYO1A inhibits Hh signaling by reducing SMURF2 expression.

Discussion

Our findings suggest that FGR is associated with a down-regulation of MYO1A, which may affect the Hh pathway through its interaction with SMURF2. This provides clues for a deeper understanding of the specific mechanisms underlying FGR.