ZMAT3 Promotes Liver Regeneration by Regulating P21 mRNA Stability to Modulate Cell Cycle

The regeneration of the liver involves a process governed by diverse biological routes. The zinc finger protein Zinc Finger MAtrin‐3 (ZMAT3) is vital in regulating transcription. This research intends to clarify how ZMAT3 influences liver regeneration and to pinpoint possible novel therapeutic intervention targets. We utilized the GEO database to examine differential gene expression and developed a liver regeneration mouse model that underwent two‐thirds partial hepatectomy. Our analysis showed that ZMAT3 expression was significantly upregulated during the phase post‐surgery. We then created a mouse model with overexpression of ZMAT3 in hepatocytes. After 2/3 hepatectomy, these mice exhibited enhanced liver regeneration, characterized by accelerated cell cycle progression and increased hepatocyte proliferation compared to controls. Bioinformatics analysis using STRING revealed a significant correlation between ZMAT3 and P21. Consistent with existing studies, we demonstrate that ZMAT3 decreases the stability of P21 mRNA, thereby reducing P21 protein levels and promoting cell cycle progression and hepatocyte proliferation, thereby enhancing liver regeneration. ZMAT3 is upregulated during the period of hepatocyte proliferation in mice and is associated with cell cycle regulation. These results suggest that ZMAT3 may serve as a potential therapeutic target to improve liver regeneration.