KLF4 inhibits colorectal cancer cell proliferation dependent on NDRG2 signaling

Ma,Yongzheng; Wu,Lin; Liu,Xuewu; Xu,Yuqiao; Shi,Wei; Liang,Ye; Yao,Libo; Zheng,Jianyong; Zhang,Jian

doi:10.3892/or.2017.5736

KLF4 inhibits colorectal cancer cell proliferation dependent on NDRG2 signaling

Authors:
- Yongzheng Ma
- Lin Wu
- Xuewu Liu
- Yuqiao Xu
- Wei Shi
- Ye Liang
- Libo Yao
- Jianyong Zheng
- Jian Zhang
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Affiliations: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Pathogenic Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, The State Key Laboratory of Cancer Biology, Department of Pathology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, The State Key Laboratory of Cancer Biology, Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, The State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/or.2017.5736
Pages: 975-984

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Abstract

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor, which was confirmed as a tumor suppressor gene in colorectal cancers. KLF4 inhibits colorectal cancer cells proliferation through upregulating p21WAF1/Cip1 and downregulating cyclin D1. We firstly reported that N-Myc downstream regulated gene 2 (NDRG2) was a novel tumor suppressor gene in multiple cancers, such as glioma, breast cancer and colorectal cancer. Herein, we provide novel evidence that KLF4 can transcriptionally activate NDRG2 by binding with NDRG2 promoter. With MTT assay, EdU staining, colony formation assay and xenograft mouse model, we confirmed that KLF4 inhibited colorectal cancer cell proliferation and tumorigenesis dependent on NDRG2. Finally, with tissue array analysis, we found a positive correlation of combined detection of KLF4/NDRG2 co-expression with TNM grades and differentiation levels of colorectal cancer. Lower expression of KLF4 and NDRG2 in colorectal cancer patients was correlated with poor overall survival. Thus, KLF4 inhibited the proliferation of colorectal cancer cells dependent on NDRG2 signaling, which provides a novel strategy for therapy and early diagnosis of colorectal cancer.

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