Icer Knockout Influences the Development of Primary Liver Cancer by Promoting Macrophage Infiltration

Introduction Inducible cAMP early repressor (ICER) modulates gene expression by binding to CREB and CREM in response to elevated cellular cAMP levels. ICER proteins can act as potent repressors of cAMP-induced gene expression. Its induction is thought to function as a negative feedback mechanism during the development of primary liver cancer. However, the specific role of ICER in liver tumor development, particularly in bone marrow-derived macrophages (BMDMs) during hepatocarcinogenesis, remains poorly understood and requires further investigation.

Methods We utilized bone marrow macrophage-specific ICER gene knockout mice to study the development of primary liver cancer after intraperitoneal injection of diethylnitrosamine (DEN). First, we compared liver cancer development between knockout and control cohorts. Next, we extracted liver tumor tissues and analyzed markers of proliferation and apoptosis. Additionally, we assessed whether ICER knockout affects macrophage infiltration in primary liver cancer tissue. Lastly, we explored potential mechanisms by which ICER influences cancer development through its regulation of macrophages.

Results Our study revealed that ICER knockout mice developed more severe primary liver cancer. Histological analysis showed a significant increase in macrophage infiltration in the tumors of ICER knockout mice, suggesting that ICER plays a regulatory role in tumor progression. Furtermore, ICER knockout altered tumor cell proliferation and apoptosis, with activation of the Wnt/beta-Catenin signaling pathway observed.

Discussion These findings underscore the critical role of ICER in hepatocarcinogenesis and suggest potential therapeutic strategies targeting ICER and its negative feedback regulation during liver cancer development.

Publication History

Article published online:
20 January 2025