C1R 已被确定在皮肤鳞状细胞癌中具有独特的功能，其功能超出了其在补体系统中的作用。然而，目前尚不清楚C1R是否参与肝细胞癌（HCC）的进展。 HCC 组织用于检查 C1R 表达与临床和病理因素的关系。通过体外和体内实验评估HCC细胞的恶性特征。通过 RNA-seq、甲基化特异性 PCR、免疫沉淀和双荧光素酶报告基因检测探索了 C1R 在 HCC 中的作用机制。本研究发现，随着HCC恶性程度的增加，C1R的表达量下降，且与预后不良相关。 C1R 启动子通过 DNMT1 和 DNMT3a 高度甲基化，导致 C1R 表达减少。 C1R 表达下调通过激活 HIF-1α 介导的糖酵解导致 HCC 细胞恶性特征增强。此外，发现 C1R 表达减少可促进异种移植肿瘤的形成。我们发现C反应蛋白（CRP）与C1R结合，游离的CRP激活NF-κB信号通路，进而增强HIF-1α的表达。 HIF-1α 的增加导致糖酵解水平升高，最终促进 HCC 的攻击行为。 C1R 启动子区域的甲基化导致 HCC 中 C1R 表达下调。 C1R 通过抑制 HIF-1α 调节的糖酵解来抑制体外和体内 HCC 的侵袭行为。这些发现表明，C1R 在 HCC 进展过程中充当肿瘤抑制基因，为创新治疗方法开辟了新的可能性。© 2024 Wiley periodicals LLC。

C1R has been identified to have a distinct function in cutaneous squamous cell carcinoma that goes beyond its role in the complement system. However, it is currently unknown whether C1R is involved in the progression of hepatocellular carcinoma (HCC). HCC tissues were used to examine C1R expression in relation to clinical and pathological factors. Malignant characteristics of HCC cells were assessed through in vitro and in vivo experiments. The mechanism underlying the role of C1R in HCC was explored through RNA-seq, methylation-specific PCR, immuno-precipitation, and dual-luciferase reporter assays. This study found that the expression of C1R decreased as the malignancy of HCC increased and was associated with poor prognosis. C1R promoter was highly methylated through DNMT1 and DNMT3a, resulting in a decrease in C1R expression. Downregulation of C1R expression resulted in heightened malignant characteristics of HCC cells through the activation of HIF-1α-mediated glycolysis. Additionally, decreased C1R expression was found to promote xenograft tumor formation. We found that C-reactive protein (CRP) binds to C1R, and the free CRP activates the NF-κB signaling pathway, which in turn boosts the expression of HIF-1α. This increase in HIF-1α leads to higher glycolysis levels, ultimately promoting aggressive behavior in HCC. Methylation of the C1R promoter region results in the downregulation of C1R expression in HCC. C1R inhibits aggressive behavior in HCC in vitro and in vivo by inhibiting HIF-1α-regulated glycolysis. These findings indicate that C1R acts as a tumor suppressor gene during HCC progression, opening up new possibilities for innovative therapeutic approaches.© 2024 Wiley Periodicals LLC.