Pcca敲低对结直肠肿瘤进展的影响
The impacts of Pcca knockdown on the colorectal tumor progression
摘要
脂质代谢重编程是癌症的一个基本特征，在肿瘤进展和免疫逃逸中发挥关键作用。我们的前期研究发现，与正常结直肠组织相比，丙酰辅酶A羧化酶α链（PCCA）在结直肠肿瘤组织中的表达显著上调，且与病人的不良预后相关。但其是否影响结直肠肿瘤免疫逃逸仍不清楚。通过构建小鼠结直肠肿瘤细胞系MC38和CT26的Pcca敲低与过表达稳转株，并在免疫健全小鼠和裸鼠中建立皮下荷瘤模型，实验结果显示：在免疫健全小鼠上，Pcca敲低显著抑制肿瘤生长，而该效应在裸鼠中消失；同时，Pcca敲低增加了瘤内CD8? T、CD4? T及NK细胞的比例，并促进巨噬细胞向M1型极化，而Pcca过表达则呈现相反作用。另外，在Ifngr1?/?小鼠中，Pcca敲低对肿瘤的抑制作用也基本消失，提示其依赖IFNγ/IFNγR1信号通路发挥抗肿瘤效应。这些结果表明，Pcca敲低可能通过激活抗肿瘤免疫和IFNγ/IFNγR1信号通路来抑制结直肠肿瘤进展。
Abstract
Lipid metabolic reprogramming is a hallmark of cancer and plays critical roles in tumor progression and immune evasion. preliminary study found that the expression of propionyl-CoA carboxylase alpha chain (PCCA) was significantly upregulated in colorectal tumor tissues compared with adjacent normal tissues, and was associated with poor prognosis of patients. However, its impacts on immune evasion in colorectal cancer remain unclear. By constructing stable Pcca knockdown and overexpression cell lines in mouse colorectal cancer cell lines MC38 and CT26, and establishing subcutaneous tumor models in immunocompetent mice and nude mice, the results showed that Pcca knockdown significantly inhibited tumor growth in immunocompetent mice, whereas this effect disappeared in nude mice. In addition, Pcca knockdown increased the infiltration of CD8? T, CD4? T, and NK cells, and promoted macrophage polarization toward an M1-like phenotype, while Pcca overexpression exhibited opposite effects. In Ifngr1?/? mice, the tumor-suppressive effect of Pcca knockdown was largely abrogated, suggesting that its function depends on the IFNγ/IFNγR1 signaling pathway. These findings indicate that Pcca knockdown may inhibit colorectal tumor progression by activating antitumor immunity and the IFNγ/IFNγR1 signaling pathway关键词
免疫学/PCCA/结直肠肿瘤/肿瘤免疫逃逸/IFNγ/IFNγR1信号通路Key words
Immunology/PCCA/Colorectal cancer/Tumor immune evasion/IFNγ/IFNγR1signaling pathway引用本文复制引用
徐鑫,黄玉辉.Pcca敲低对结直肠肿瘤进展的影响[EB/OL].(2026-06-16)[2026-06-18].http://www.paper.edu.cn/releasepaper/content/202606-50.学科分类
肿瘤学/基础医学/生物化学/生物科学研究方法、生物科学研究技术
