Mechanism of microRNA‐152 Regulating Decidual Natural Killer Cell Viability and Affecting Trophoblast Cell Invasiveness via the HLA‐G/KIR2DL4 Axis

TL;DR

This study shows how miR-152 affects dNK cell function and trophoblast invasion through the HLA-G/KIR2DL4 pathway, which is important for maintaining pregnancy.

Contribution

The study reveals a novel regulatory mechanism involving miR-152, HLA-G, and KIR2DL4 in pregnancy-related cell interactions.

Findings

miR-152 overexpression reduces dNK cell cytokine secretion and trophoblast cell viability and invasion.

miR-152 directly targets HLA-G, and its inhibition reverses these effects.

Blocking HLA-G/KIR2DL4 interaction counteracts the impact of miR-152 on dNK and trophoblast cells.

Abstract

Trophoblast cells are specialized placental epithelial cells essential for pregnancy maintenance. miR‐152 is implicated in trophoblast cell regulation and pregnancy failure. This study explores the role of miR‐152 in decidual natural killer (dNK) cell viability and trophoblast cell invasion. HTR‐8/SVneo cells were transfected with miR‐152‐mimics/inhibitor or their respective controls, followed by co‐culture with dNK cells. RT‐qPCR assessed transfection efficiency, while cytokine secretion (IL‐8, IP‐10, VEGF), cell viability, apoptosis, and invasion were evaluated via ELISA, CCK‐8, flow cytometry, Western blot, and Transwell assays. The interaction between miR‐152 and HLA‐G was examined via dual‐luciferase reporter assay, and HLA‐G/sHLA‐G levels were measured. Co‐cultures of dNK cells and miR‐152/HLA‐G‐overexpressing HTR‐8/SVneo cells were established, and anti‐KIR2DL4/IgG1 was used to block HLA‐G/KIR2DL4 binding. Co‐immunoprecipitation confirmed protein interactions. miR‐152 overexpression suppressed dNK cell cytokine secretion, reduced HTR‐8/SVneo cell viability and invasion, and promoted apoptosis. miR‐152 inhibition had the opposite effect. miR‐152 directly targeted HLA‐G, and HLA‐G overexpression rescued dNK function and trophoblast invasion. Blocking the HLA‐G/KIR2DL4 binding counteracted the effects of miR‐152. miR‐152 inhibits dNK cell function and trophoblast invasion by targeting HLA‐G, reducing HLA‐G/KIR2DL4 interaction. These findings highlight a potential regulatory mechanism in pregnancy maintenance.

Figures