Mechanism of KLF11 in promoting angiogenesis and affecting metastasis and invasion of colorectal cancer by regulating Akt/MDM2/p53 signaling pathway
10.3760/cma.j.cn115396-20250207-00023
- VernacularTitle:KLF11通过调控Akt/MDM2/p53信号通路促进结直肠癌血管生成及影响其转移及侵袭的机制研究
- Author:
Danlu LIU
1
;
Futao WANG
Author Information
1. 西安市中心医院肛肠外科，西安 710000
- Keywords:
Colorectal neoplasms;
Cell proliferation;
HCT116 cells;
KLF11
- From:
International Journal of Surgery
2025;52(5):307-312
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism of KLF11 in the angiogenesis, metastasis, and invasion of colorectal cancer (CRC) by regulating the Akt/MDM2/p53 signaling pathway.Methods:Human colorectal cancer cells HCT-116 and normal colorectal mucosal epithelial cells FHC were routinely cultured, and HCT-116 cells were divided into control, pc-DNA3.1-NC, pc-DNA3.1-KLF11, and pc-DNA3.1-KLF11 + SC79 groups, and the pc-DNA3.1-KLF11 overexpression vector was transfected into the corresponding groups. KLF11 expression in CRC tissues and normal colorectal tissues was analyzed using an online tool called gene expression profiling interactive analysis (GEPIA). RT-qPCR and protein immunoblotting (WB) were used to detect changes in KLF11 expression levels and related proteins.CCK-8, cell scratch assay, and Transwell assay were used to assess cell viability, migration, and invasion ability. An angiomimetic formation assay was performed to observe angiogenesis. Western blot assay was performed to detect the effect of KLF11 on the Akt/MDM2/p53 pathway, metastasis, invasion, and angiogenesis-related protein expression. The experimental data were repeated 3 times, and the single-factor analysis of variance (ANOVA) was used for multiple group comparison, and LSD or Tamhare T2 test was used for pairwise comparison. Results:GEPIA analysis showed that KLF11 was lowly expressed in colon adenocarcinoma and rectal adenocarcinoma. KLF11 overexpression significantly decreased the viability, migration, and invasion ability of HCT-116 cells and reduced the number of angiogenesis. WB results showed that KLF11 overexpression affected the expression of key proteins in the Akt/MDM2/p53 signaling pathway, including decreased p-Akt, p-MDM2, Vimentin, VEGF, and HIF1-α proteins, while increasing the expression of p53 and E-cadherin proteins. The expression levels of the relevant proteins were reversed after treatment with the Akt inhibitor SC79.Conclusion:KLF11 inhibits the proliferative activity, migration, invasion, and angiogenesis of colorectal cancer cells by regulating the Akt/MDM2/p53 signaling pathway and may be a potential target for CRC therapy.
