Circular RNA circLAMC1 Promotes Liver Regeneration by Regulating the miR ‐138‐5p/Gnai2 Axis

Liver regeneration from acute injury is well-studied, and various factors and pathways are known to be involved. Circular RNAs (circRNAs) are emerging as critical regulators in liver pathophysiology, yet their roles in liver regeneration remain unclear. Here, we characterized a circular RNA, circLAMC1, which was highly upregulated in rats after partial hepatectomy (PH). Overexpression of circLAMC1 promoted liver cell proliferation in vitro. Further mechanistic studies revealed that circLAMC1 interacted with the microRNA miR-138-5p, and that miR-138-5p directly targeted Gnai2. While miR-138-5p mimics or Gnai2 knockdown repressed the proliferative effects mediated by circLAMC1, inhibition of miR-138-5p or Gnai2 upregulation enhanced liver cell proliferation. In vivo, AAV9-mediated circLAMC1 overexpression in mice increased the liver/body weight ratio, reduced liver injury, and increased the number of hepatocytes after PH. Furthermore, circLAMC1 activated the ERK signaling pathway through the miR-138-5p/Gnai2 axis, ultimately upregulating cell cycle proteins. Collectively, our data reveal a specific role for circLAMC1 in liver regeneration and provide a potential regulatory target for promoting liver regeneration after injury.