CBX7 silencing promoted liver regeneration by interacting with BMI1 and activating the Nrf2/ARE signaling pathway

• Published in: Scientific reports 2024-05, Vol.14 (1), p.11008-12, Article 11008
• Main Authors: Dou, Zhimin, Lu, Fei, Hu, Jinjing, Li, Bin, Li, Xun
• Format: Article
• Language: English
• Subjects: 631/337; 631/80; Animals; Apoptosis; Apoptosis - genetics; BMI1; Body weight; CBX7; Cell cycle; Cell Proliferation; Gene Silencing; Hepatectomy; Hepatocytes; Hepatocytes - metabolism; Humanities and Social Sciences; Liver; Liver - metabolism; Liver regeneration; Liver Regeneration - genetics; Male; Mice; Mice, Inbred C57BL; multidisciplinary; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Science; Science (multidisciplinary); Signal Transduction; siRNA
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-58248-8

Multiple studies have shown knockdown of chromobox 7 (CBX7) promotes the regenerative capacity of various cells or tissues. We examined the effect of CBX7 on hepatocyte proliferation and liver regeneration after 2/3 hepatectomy in a mouse model. For in vitro experiments, NCTC 1469 and BNL CL.2 hepatocytes were co-transfected with siRNA-CBX7-1 (si-CBX7-1), siRNA-CBX7-2 (si-CBX7-2), pcDNA-CBX7, si-BMI1-1, si-BMI1-2, pcDNA-BMI1, or their negative control. For in vivo experiments, mice were injected intraperitoneally with lentivirus-packaged shRNA and shRNA CBX7 before hepatectomy. Our results showed that CBX7 was rapidly induced in the early stage of liver regeneration. CBX7 regulated hepatocyte proliferation, cell cycle, and apoptosis of NCTC 1469 and BNL CL.2 hepatocytes. CBX7 interacted with BMI1 and inhibited BMI1 expression in hepatocytes. Silencing BMI1 aggregated the inhibitory effect of CBX7 overexpression on hepatocyte viability and the promotion of apoptosis. Furthermore, silencing BMI1 enhanced the regulatory effect of CBX7 on Nrf2/ARE signaling in HGF-induced hepatocytes. In vivo, CBX7 silencing enhanced liver/body weight ratio in PH mice. CBX7 silencing promoted the Ki67-positive cell count and decreased the Tunel-positive cell count after hepatectomy, and also increased the expression of nuclear Nrf2, HO-1, and NQO-1. Our results suggest that CBX7 silencing may increase survival following hepatectomy by promoting liver regeneration.