Department of General Surgery, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Hepatobiliary and Pancreatic (HBP) Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Cell Cycle. 2024 Mar;23(6):682-692. doi: 10.1080/15384101.2024.2355825. Epub 2024 May 24.
Pumilio RNA-binding family member 1 (PUM1) has been implicated in both the progression of colorectal cancer and the regulation of inflammation. The role of PUM1 in the polarization of tumor-associated macrophages (TAMs) into the M2 phenotype has not yet been reported in hepatocellular carcinoma. Using the PUM1-knockout mice model, flow cytometry, and IHC, we validated the role of PUM1 in hepatocellular carcinoma (HCC) TAMs. One-way analysis of variance (ANOVA) or student's t-tests was used to compare the experimental groups. We found that PUM1 inhibited anti-tumor immunity in HCC through TAM-mediated inhibition of CD8+ T cells. We also showed that PUM1 promotes the transformation of TAMs into pro-tumorigenic M2-like phenotypes by activating cAMP signaling pathway. This study emphasized the potential of PUM1 as a target for immunotherapy in HCC through TAMs. The present study revealed the molecular mechanism underlying the pro-tumor role of PUM1 in HCC.
Pumilio RNA-binding family member 1 (PUM1) 已被牵连到结直肠癌的进展和炎症的调节中。在肝细胞癌中，PUM1 在肿瘤相关巨噬细胞（TAMs）向 M2 表型极化中的作用尚未被报道。使用 PUM1 敲除小鼠模型、流式细胞术和免疫组化，我们验证了 PUM1 在肝细胞癌（HCC）TAMs 中的作用。采用单因素方差分析（ANOVA）或学生 t 检验比较实验组。我们发现 PUM1 通过 TAM 介导的抑制 CD8+T 细胞来抑制 HCC 的抗肿瘤免疫。我们还表明，PUM1 通过激活 cAMP 信号通路促进 TAMs 向促肿瘤发生的 M2 样表型转化。这项研究强调了通过 TAMs 将 PUM1 作为 HCC 免疫治疗靶点的潜力。本研究揭示了 PUM1 在 HCC 中促肿瘤作用的分子机制。
