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hsa_circ_0081343 interacts with Rbm8a to inhibit NLRP3-mediated pyroptosis via the PI3K/AKT/HIF-1α pathways

Linmei Zheng1, Rong Tang2, Fiaz Ahmad3

  • 1Department of Obstetrics, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China; Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Placenta
|April 23, 2025
PubMed

Insights

This study reveals that hsa_circ_0081343 and Rbm8a interaction regulates NLRP3-mediated pyroptosis in fetal growth restriction (FGR). Their interplay impacts the PI3K/AKT/HIF-1α pathway, offering new insights into FGR pathogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Reproductive Biology

Background:

  • Pyroptosis at the maternal-fetal interface is implicated in fetal growth restriction (FGR).
  • hsa_circ_0081343 acts as an RNA-binding protein sponge, potentially regulating Rbm8a nuclear transport.
  • Understanding the interaction between hsa_circ_0081343 and Rbm8a in FGR pyroptosis is crucial.

Purpose of the Study:

  • To elucidate the regulatory mechanism of hsa_circ_0081343 and Rbm8a interaction in the FGR pyroptosis pathway.
  • To investigate the role of this interaction in the PI3K/AKT/HIF-1α signaling pathway.
  • To explore the potential of targeting this pathway for FGR treatment.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR), Western blot, and ELISA for pathway component and cytokine analysis.
  • RNA sequencing (RNA-seq) and Chromatin immunoprecipitation sequencing (ChIP-seq) to identify downstream targets.
  • RNA pull-down assays to confirm direct interactions between hsa_circ_0081343 and Rbm8a.

Main Results:

  • Fetal growth restriction (FGR) placentas showed increased NLRP3 expression.
  • hsa_circ_0081343 overexpression inhibited pyroptosis and inflammation, effects reversed by Rbm8a knockdown.
  • The PI3K/AKT and HIF-1α pathways were identified as targets, with their activity inversely correlated to hsa_circ_0081343/Rbm8a levels. Rbm8a binds hsa_circ_0081343 and modulates its formation.

Conclusions:

  • The hsa_circ_0081343-Rbm8a interaction regulates NLRP3-mediated pyroptosis via the PI3K/AKT/HIF-1α pathway in FGR.
  • Rbm8a directly binds hsa_circ_0081343, influencing its biogenesis.
  • This study provides novel insights into circRNA-RBP regulatory mechanisms in FGR pathogenesis.
Abstract

Keywords:
Fetal growth restrictionNLRP3PI3K-AKT pathwayPyroptosisRbm8ahsa_circ_0081343

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