Research Paper Volume 16, Issue 3 pp 2475—2493

KLF3 promotes colorectal cancer growth by activating WNT1

Wei Shen1, , Lebin Yuan1, *, , Boyu Hao2, *, , Jiajia Xiang3, *, , Fei Cheng1, , Zhao Wu1, , Xiaodong Li1, ,

  • 1 Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
  • 2 General Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
  • 3 Laboratory of Molecular Center, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
* Equal contribution

Received: August 17, 2023       Accepted: December 26, 2023       Published: February 1, 2024
How to Cite

Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Objective: The function of Kruppel-like factor 3 (KLF3) remains largely unexplored in colorectal cancer (CRC).

Methods: KLF3 expression in CRC was assessed through qPCR, western blotting, immunohistochemical assays, and The Cancer Genome Atlas (TCGA) database. The tumor-promoting capacity of KLF3 was explored by performing in vitro functional experiments using CRC cells. A subcutaneous nude mouse tumor assay was employed to evaluate tumor growth. To further elucidate the interaction between KLF3 and other factors, luciferase reporter assay, agarose gel electrophoresis, and ChIP analysis were performed.

Results: KLF3 was downregulated in CRC tissue and cells. Silencing of KLF3 increased the potential of CRC cells for proliferation, migration, and invasion, while its activation decreased these processes. Downregulated KLF3 was associated with accelerated tumor growth in vivo. Mechanistically, KLF3 was discovered to target the promoter sequence of WNT1. Consequently, the diminished expression of KLF3 led to the buildup of WNT1 and the WNT/β-catenin pathway activation, consequently stimulating the progression of CRC.

Conclusions: This investigation suggests that the involvement of KLF3/WNT1 regulatory pathway contributes to the progression of CRC, thereby emphasizing its promise as an important focus for future therapies aimed at treating CRC.


KLF3: Kruppel-like factor 3; WNT1: wingless-type MMTV integration site family, member 1; CRC: colorectal cancer; TCGA: The Cancer Genome Atlas; qRTPCR: quantitative real time polymerase chain reaction; CHIP: Chromatin immunoprecipitation; IHC: Immunohistochemistry; GSEA: Gene Set Enrichment Analysis; TME: tumor microenvironment..