# Circ-104792/miR-133a/Bcl-xL influences the proliferation and function of human trophoblastic and decidual stromal cells involved in recurrent abortion disease

## TL;DR

This study identifies a molecular pathway involving circ-104792, miR-133a, and Bcl-xL that affects cell function in recurrent abortion, offering new insights for diagnosis and treatment.

## Contribution

The study reveals a novel regulatory axis (circ-104792/miR-133a/Bcl-xL) involved in recurrent abortion and its impact on trophoblastic and decidual stromal cell function.

## Key findings

- miR-133a is upregulated and circ-104792 is downregulated in RSA tissues, affecting cell proliferation and apoptosis.
- circ-104792 overexpression counteracts miR-133a's effects by acting as a ceRNA and increasing Bcl-xL expression.
- The miR-133a/circ-104792/Bcl-xL axis is a potential therapeutic target for RSA.

## Abstract

The circRNA-miRNA axis is critically implicated in the pathogenesis of recurrent spontaneous abortion (RSA) by modulating trophoblast and decidual stromal cell functions. This study investigates the role of the miR-133a/circ-104792 network in RSA.

Using qRT-PCR, we measured miR-133a and circ-104792 expression in chorion and decidua from 10 RSA patients and 10 controls. The functional effects on proliferation (CCK-8, EdU) and apoptosis (flow cytometry, TUNEL) were assessed in HTR-8/SVneo and HESC cells following transfection with miR-133a mimics/inhibitor or circ-104792. Direct targeting of Bcl-xL by miR-133a and its interaction with circ-104792 were validated via dual-luciferase reporter and RNA pull-down assays. Bcl-xL expression was evaluated by qRT-PCR and western blot.

miR-133a expression was (in chorion: p = 0.0008, 95% CI [2.85, 6.41]; in decidua: p = 0.0009, 95% CI [2.67, 6.03]) increased, while circ-104792 was significantly downregulated (in chorion: p = 0.0008, 95% CI [0.15, 0.34]; in decidua: p = 0.0007, 95% CI [0.13, 0.31]) in RSA tissues. In vitro, miR-133a overexpression inhibited cell proliferation, promoted apoptosis, and reduced Bcl-xL levels (in HTR-8/SVneo: 0.46-fold vs. 1.00 in NC group, p = 0.0045; in HESCs: 0.49-fold vs. 1.00 in NC group, p = 0.0003). Conversely, circ-104792 overexpression enhanced proliferation, suppressed apoptosis, and increased Bcl-xL expression (in HTR-8/SVneo: 2.17-fold vs. 1.00 in vector group, p = 0.0018; in HESCs: 1.94-fold vs. 1.00 in vector group, p = 0.0015). The dual-luciferase assay confirmed Bcl-xL as a direct target of miR-133a, and the RNA pull-down confirmed the miR-133a/circ-104792 interaction. Critically, circ-104792 overexpression rescued the suppressive effects of miR-133a on proliferation and Bcl-xL expression.

Our findings demonstrate that miR-133a promotes RSA-associated cellular dysfunction by targeting Bcl-xL, while circ-104792 acts as a ceRNA to sponge miR-133a, thereby antagonizing its effects. The miR-133a/circ-104792/Bcl-xL axis represents a potential key regulatory network in RSA, presenting potential novel targets for diagnosis and therapy.