Journal Article

Mechanism of miR-20b-5p targeting HIF-1α in regulating trophoblast function in recurrent spontaneous abortion

Fu, Aizhen, Guo, Yihong, Lai, Yanyu, Wu, Qiaoxian, Chen, Lujing

2025

Overview

Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1α in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1α were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1α to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1α. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1α expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1α was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1α, contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1α axis may serve as a potential therapeutic target for RSA.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Abortion, Habitual - genetics / Abortion, Habitual - metabolism / Abortion, Habitual - pathology / Adult / Apoptosis / Apoptosis - genetics / Biomedicine / Case-Control Studies / Cell adhesion & migration / Cell culture / Cell Movement - genetics / Diabetes / Endocrine disorders / Female / Fertility / Flow cytometry / HIF-1α / Humans / Hypoxia / Hypoxia-Inducible Factor 1, alpha Subunit - genetics / Hypoxia-Inducible Factor 1, alpha Subunit - metabolism / Infectious Diseases / Insulin resistance / Internal Medicine / Medical research / Medicine / Medicine & Public Health / Metabolism / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / MiR-20b-5p / Miscarriage / Oncology / Penicillin / Pregnancy / Pregnancy complications / Recurrent spontaneous abortion / Surgery / Trophoblast / Trophoblasts - metabolism / Trophoblasts - pathology / Trophoblasts - physiology / Womens health