Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1

Zhang,Jie; Wang,Ye; Hou,Shiyang; Chi,Xiaoqian; Ding,Danyang; Xue,Mei; Zhang,Mengqiao; Wang,Jing; Shuai,Junfang; Sun,Haiying; Gao,Qiang; Kang,Chunbo

doi:10.3892/or.2024.8741

Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1

Authors:
- Jie Zhang
- Ye Wang
- Shiyang Hou
- Xiaoqian Chi
- Danyang Ding
- Mei Xue
- Mengqiao Zhang
- Jing Wang
- Junfang Shuai
- Haiying Sun
- Qiang Gao
- Chunbo Kang
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Affiliations: Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China, Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
Published online on: April 23, 2024 https://doi.org/10.3892/or.2024.8741
Article Number: 82
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The 5‑year survival rate of patients diagnosed with the early stages of the disease is markedly higher than that of patients in the advanced stages. Therefore, identifying novel biomarkers and drug targets for CRC is critical for clinical practice. Zinc finger protein 169 (ZNF169) is a crucial transcription factor, and its role in CRC remains to be explored. The present study aimed to investigate the clinical relevance, function and underlying mechanisms of ZNF169 in CRC growth and proliferation. The Cancer Genome Atlas (TCGA) database was utilized to analyze the clinical relevance of ZNF169 in patients with CRC. Immunohistochemical staining was performed on tissue samples from patients with CRC to detect the expression of ZNF169. The HCT‑116, HT‑29 and RKO cell lines were employed for in vitro experiments. The overexpression and knockdown of ZNF169 were achieved by transfecting the cells with lentivirus and small interfering RNAs, respectively. Cell Counting Kit‑8, colony formation and EdU staining assays were applied to investigate the function of ZNF169 in CRC cells. Dual luciferase activity and chromatin immunoprecipitation (ChIP)‑quantitative PCR (qPCR) assays were performed to identify the regulatory effects of ZNF169 on the ankyrin repeat and zinc‑finger domain‑containing 1 (ANKZF1; also known as ZNF744) gene. Reverse transcription‑quantitative PCR and western blot analysis were performed to measure mRNA and protein expression, respectively. The analysis of TCGA data revealed a positive correlation between ZNF169 and ANKZF1, with the overexpression of ANKZF1 being associated with a poor prognosis of patients with CRC. The experimental results demonstrated that ZNF169 was expression upregulated in CRC tissue compared with that in normal colon tissue. Gain‑of‑function and loss‑of‑function experiments revealed that ZNF169 enhanced the intensity of EdU staining, promoting the growth and proliferation of CRC cells. Furthermore, the overexpression of ZNF169 potentiated the transcriptional activity of the ANKZF1 gene, while the knockdown of ZNF169 produced the opposite results. ChIP‑qPCR confirmed the interaction between ZNF169 and the promoter sequence of ANKZF1. Rescue experiments revealed that ZNF169 accelerated CRC cell growth and proliferation through the upregulation of ANKZF1. Furthermore, there was a positive correlation identified between ZNF169 and ANKZF1, and upregulation of ANKZF1 expression was associated with the poor prognosis of patients with CRC. On the whole, the present study demonstrates that ZNF169 contributes to CRC malignancy by potentiating the expression of ANKZF1. Thus, the regulation of ZNF169 and/or ANKZF1 expression may represent a viable strategy for the treatment patients with CRC with a high expression of ZNF169.

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