Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment

Na LUO; Dapeng ZHANG; Hongming MIAO; Rongyang DAI

doi:10.16016/j.1000-5404.202106129

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Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment

Basic Medicine | 更新时间：2026-01-09

- Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment
- Journal of Third Military Medical University Vol. 43, Issue 24, Pages: 2648-2655(2021)
- 作者机构：
  
  1.646000 四川泸州，西南医科大学基础医学院
  2.400038 重庆，陆军军医大学(第三军医大学)基础医学院生物化学与分子生物学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81872028)
- DOI：10.16016/j.1000-5404.202106129
  CLC： R345;R730.23;R735.35
- Received：17 June 2021，
  
  Revised：2021-09-22，
  
  Published：30 December 2021
- 稿件说明：
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Na LUO, Dapeng ZHANG, Hongming MIAO, et al. Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment[J]. Journal of Third Military Medical University, 2021, 43(24): 2648-2655.
DOI：

Na LUO, Dapeng ZHANG, Hongming MIAO, et al. Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment[J]. Journal of Third Military Medical University, 2021, 43(24): 2648-2655. DOI： 10.16016/j.1000-5404.202106129.

摘要

目的

研究法呢基二磷酸酯法呢基转移酶1 (farnesyl-diphosphate farnesyltransferase 1，FDFT1)对结肠癌(colorectal cancer，CRC)细胞MC-38体内体外生长的影响。

方法

通过GEPIA数据库分析275例CRC样本和349例正常组织样本中FDFT1的表达量，通过数据库分析人CRC中FDFT1的免疫组化表达水平。使用慢病毒介导的短发夹RNA(short hairpin RNA，shRNA)构建FDFT1沉默的CRC细胞系MC-38，得到稳定低表达FDFT1的MC-38细胞系(sh-FDFT1组)和空载对照细胞系(sh-NC组)，Western blot、RT-qPCR验证敲低效果。CCK-8实验、流式细胞术、Transwell实验分别观察敲低FDFT1对MC-38细胞增殖、凋亡、迁移能力的影响。采用C57BL/6小鼠、重度免疫缺陷NCG小鼠构建CRC腹腔种植转移模型，利用C57BL/6小鼠构建皮下移植瘤模型，14 d后观察沉默FDFT1对小鼠肿瘤生长情况的影响。

结果

数据库分析结果显示CRC组织中FDFT1的表达较正常组织高(

0.05)，免疫组化结果显示CRC病人FDFT1高表达。沉默FDFT1对MC-38细胞增殖、凋亡及迁移均没有明显影响；在C57BL/6小鼠CRC腹腔种植转移模型和皮下移植瘤模型中均发现沉默FDFT1后显著抑制肿瘤生长(

0.05)。NCG小鼠腹腔种植转移模型显示沉默FDFT1后肿瘤生长没有差异(

0.05)。

结论

FDFT1在体内促进CRC细胞生长依赖于肿瘤免疫微环境。

Abstract

Objective

To investigate the effects of farnesyl-diphosphate

farnesyltransferase 1 (FDFT1) on the growth of colorectal cancer (CRC) cell line MC-38

in vitro

and in mouse models of colorectal peritoneal metastasis and xenograft tumor.

Methods

The expression of FDFT1 in 275 CRC samples and 349 normal tissue samples

as well as the immunohistochemical expression level of FDFT1 in human CRC tissues were analyzed using online databases Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas

respectively. FDFT1-silenced CRC cell line MC-38 was constructed by lentivirus-mediated short hairpin RNA (shRNA) to obtain stable cells with low expression of FDFT1 (sh-FDFT1)

and blank control cells (sh-NC) was also constructed. The knockdown effect was subsequently verified by Western blotting and RT-qPCR. Cell counting kit-8 (CCK-8) assay

flow cytometry and transwell assay were performed to observe the effects of FDFT1 knockdown on the proliferation

apoptosis and migration of MC-38 cells

respectively. In addition

intraperitoneal implantation models of colorectal cancer were established using C57BL/6 mice and severe immunodeficient NCG mice

and subcutaneous transplantation tumor model was also constructed using C57BL/6 mice. The effects of FDFT1 silencing on tumor growth

in vivo

were observed in 14 d after transplantation.

Results

Database analysis showed that FDFT1 expression was higher in CRC tissues than normal tissues (

0.05)

and immunohistochemical results also confirmed that FDFT1 was highly expressed in CRC tissues. There were no significant alterations in the proliferation

apoptosis and migration of MC-38 cells after knockdown of FDFT1. Although FDFT1 silencing obviously inhibited the tumor growth in both intraperitoneal implantation and subcutaneous xenograft models of CRC in C57BL/6 mice (

0.05)

the colorectal peritoneal metastasis model of NCG mice presented no difference in tumor growth after silenci

ng FDFT1 (

0.05).

Conclusion

FDFT1 depends on the tumor immune microenvironment in the promotion of the growth of CRC cells

in vivo

关键词

Keywords

references

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