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Updated: Aug 23, 2025

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
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In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions

Published on: October 21, 2022

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Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair

Peng Wang1, Zhitao Huang1, Yili Peng1

  • 1Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China.

Nature Communications
|November 1, 2022
PubMed

Insights

Circular RNA circBNC2 normally prevents epithelial cell cycle arrest after injury. Restoring circBNC2 reduces fibrosis in kidney and liver, offering a potential therapeutic strategy for fibrotic diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Organ Fibrosis Research

Background:

  • Fibrotic responses after injury are poorly understood.
  • Epithelial cell cycle arrest at G2/M is a critical determinant of wound healing outcomes, influencing normal proliferation or fibrosis.
  • Identifying key regulators of this checkpoint is crucial for understanding and treating fibrotic diseases.

Purpose of the Study:

  • To identify novel regulators of epithelial cell cycle arrest in the context of organ injury and fibrosis.
  • To investigate the role of a specific circular RNA, circBNC2, in fibrotic responses.
  • To explore the therapeutic potential of circBNC2 in mitigating kidney and liver fibrosis.

Main Methods:

  • Identification and characterization of circBNC2 expression in normal and injured kidney and liver tissues.
  • In vitro and in vivo gain- and loss-of-function studies to assess circBNC2's role in cell cycle regulation.
  • Experimental induction of kidney and liver fibrosis in male mouse models.
  • Analysis of cell cycle markers, fibrotic factors, and extracellular matrix deposition.
  • Correlation of findings with human samples of chronic kidney disease and liver fibrosis.

Main Results:

  • circBNC2, a kidney- and liver-enriched circular RNA, is downregulated after injury, partly due to DHX9 upregulation.
  • circBNC2 functions as a negative regulator of G2/M arrest by promoting CDK1/cyclin B1 complex formation.
  • Restoring circBNC2 in mouse models reduced G2/M arrested cells, fibrotic factor secretion, and extracellular matrix deposition, thereby mitigating fibrosis.
  • Reduced circBNC2 and increased G2/M arrest were observed in human fibrotic conditions.

Conclusions:

  • circBNC2 plays a critical role in preventing epithelial cell G2/M arrest and subsequent fibrosis.
  • Loss of circBNC2 is a significant factor in the development of kidney and liver fibrosis.
  • Restoring circBNC2 represents a promising therapeutic avenue for treating epithelial organ fibrosis.

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