Clinical significance and biological role of KLF17 as a tumour suppressor in colorectal cancer

Jiang,Xun; Shen,Tong‑Yi; Lu,Helei; Shi,Chenzhang; Liu,Zhongchen; Qin,Huanlong; Wang,Feng

doi:10.3892/or.2019.7324

Clinical significance and biological role of KLF17 as a tumour suppressor in colorectal cancer

Authors:
- Xun Jiang
- Tong‑Yi Shen
- Helei Lu
- Chenzhang Shi
- Zhongchen Liu
- Huanlong Qin
- Feng Wang
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Affiliations: Department of General Surgery, Affiliated Shanghai Tenth Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, P.R. China
Published online on: September 18, 2019 https://doi.org/10.3892/or.2019.7324
Pages: 2117-2129

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Abstract

It has been reported that kruppel‑like factor 17 (KLF17) acts as a tumour suppressor in several tissues and cancer cells, however, the molecular roles, the underlying mechanisms and clinical significance of KLF17 in colorectal cancer (CRC) have not been completely elucidated. In the present study, KLF17 protein expression was detected in 140 primary CRCs and paired adjacent non‑tumour tissues using immunohistochemistry with tissue microarrays. The KLF17 mRNA expression was determined in 4 CRC cell lines and 20 pairs of the aforementioned tissues using reverse transcription quantitative polymerase chain reaction. The correlation between KLF17 expression and clinicopathologic characteristics was determined. Next, the functions of KLF17 in CRC were examined by cell proliferation, colony formation, adhesion, invasion and mouse xenograft assays. Methylation‑specific PCR and bisulfite sequencing PCR were also carried out to investigate the promoter methylation status of KLF17 in CRC cells and tissues and explore the effects of lentiviral‑mediated RNAi of UHRF1 on the methylation and expression of KLF17. The results revealed that KLF17 expression was abnormally decreased in CRC and associated with lymph node metastasis and unfavorable overall survival. Moreover, ectopic KLF17 expression suppressed CRC cell growth and invasion in vitro and in vivo. In addition, the downregulation of KLF17 was associated with the hypermethylation of the CpG nucleotides on the KLF17 promoter. The knockdown of the epigenetic regulator UHRF1 reduced the methylation level of the KLF17 promoter and inhibited CRC cell adhesion, invasion and epithelial‑mesenchymal transition by upregulating KLF17. The present findings indicated that KLF17 may act as a tumour suppressor gene in CRC and a potential independent prognostic biomarker in CRC patients. UHRF1 can suppress KLF17 expression through the hypermethylation of its promoter in CRC. These results offer insights into the KLF17 expression regulation in CRC and suggest an inhibitory effect of KLF17 on tumourigenesis.

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