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中国癌症防治杂志

中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (1): 28-33.doi: 10.3969/j.issn.1674-5671.2021.01.05

• 消化道肿瘤专栏 • 上一篇    下一篇

CASC19通过维持巨噬细胞M1型极化状态保持对结直肠癌的抑制作用

  

  1. 首都医科大学附属北京世纪坛医院消化科；首都医科大学附属北京友谊医院消化分中心，国家消化系统疾病临床医学研究中心，消化疾病癌前病变北京市重点实验室，北京消化中心；首都医科大学附属北京同仁医院科技处
  • 出版日期:2021-02-25 发布日期:2021-03-05
  • 通讯作者: 吴静 E-mailwujing36@163.com
  • 基金资助:
    首都医科大学附属北京友谊医院博士生导师专项计划项目 （YYDSZX201901）；北京市医院管理中心消化内科学科协同发展中心细化专项重点项目（XXZ0105）

Inhibitory effect of CASC19 on colorectal cancer through maintaining macrophage M1 polarization

  • Online:2021-02-25 Published:2021-03-05
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摘要： 目的 探讨长链非编码RNA癌症易感基因19（the cancer susceptibility 19，CASC19）在维持巨噬细胞M1型极化状态中的作用及其对结直肠癌细胞生长的影响。方法 诱导单核细胞型淋巴瘤细胞Thp1分化为未极化的M0巨噬细胞，进一步诱导M0极化为经典活化的M1巨噬细胞和替代性活化的M2巨噬细胞；采用RT-qPCR检测M1和M2相关分子标记和CASC19的表达，明确巨噬细胞分化状态及CASC19转染效率；使用敲降CASC19的M1型巨噬细胞上清（M1 SI-CM组）及其阴性对照上清（M1 NC-CM组）刺激结直肠癌细胞SW480，采用活细胞实时动态成像、MTS法检测细胞增殖能力，Transwell检测细胞迁移能力。结果 RT-qPCR检测结果显示，巨噬细胞诱导极化成功，且CASC19在M1型巨噬细胞中的表达水平高于M0型和M2型（P<0.05）；与M1 NC-CM组处理相比，CASC19敲降的M1 SI-CM处理组对结直肠癌细胞SW480增殖和迁移能力的抑制作用更弱（P<0.001）；敲降M1型巨噬细胞中的CASC19后M1分子标记CD40、IL-1β的表达均降低，而M2分子标记CD206、IL-10、CD163的表达水平升高（P<0.05）。结论 敲降CASC19能减弱M1型巨噬细胞抑制结直肠癌细胞增殖、迁移功能，可能是通过解除CASC19对巨噬细胞M1极化状态的维持作用实现。

关键词: 结直肠癌, 巨噬细胞, 长链非编码RNA, CASC19, 极化状态

Abstract: Objective To investigate the role of long non-coding RNA CASC19(the cancer susceptibility 19) in maintaining the polarized state of M1 macrophage and its effect on the growth of colorectal cancer cells. Methods Mononuclear lymphoma Thp1 cells were induced to degenerate into unpolarized macrophage M0, which were further induced to polarize into the classical activated M1 macrophage and the alternative activated M2 macrophage. The expressions of the M1 and M2 macrophage molecular markers and the CASC19 were detected by RT-qPCR, and the polarized state of macrophages and transfection efficiency of CASC19 were confirmed. The colorectal cancer cells SW480 were stimulated by the supernatant of M1 macrophage(M1 SI-MC group) and Negative control supernatant(M1 NC-MC group) that knocked down CASC19. Real-time dynamic imaging and MTS staining were used to assess the cell proliferation ability, and Transwell assays was used to measure the cell migration ability. Results RT-qPCR showed that polarized macrophages were successfully induced. The expression level of CASC19 in M1 macrophage was higher than that in M0 and M2 macrophage(P<0.05). Compared with the M1 NC-CM group, the supernatant of M1 macrophage with knocking down CASC19 had weaker inhibition on the proliferation and migration of colorectal cancer cells SW48（P<0.001）. After knocking down CASC19 in M1 macrophage, the expression levels of M1 molecular markers CD40 and IL-1β were decreased, while the expression levels of M2 molecular markers CD206, IL-10 and CD163 were increased(P<0.05). Conclusion CASC19 knockdown can weaken the inhibition of proliferation and migration of M1 macrophage on colorectal cancer cells, which may be achieved by eliminating the maintenance effect of CASC19 on the polarized state of M1 macrophage.

Key words:  , Colorectal cancer, Macrophages, Long non-coding RNA, CASC19, Polarized

中图分类号: 

  • R735.3