ZNF692 promotes colon adenocarcinoma cell growth and metastasis by activating the PI3K/AKT pathway

Xing,Yanwei; Ren,Shuo; Ai,Lianjie; Sun,Weidong; Zhao,Zhiwei; Jiang,Fengqi; Zhu,Yuekun; Piao,Daxun

doi:10.3892/ijo.2019.4733

ZNF692 promotes colon adenocarcinoma cell growth and metastasis by activating the PI3K/AKT pathway

Authors:
- Yanwei Xing
- Shuo Ren
- Lianjie Ai
- Weidong Sun
- Zhiwei Zhao
- Fengqi Jiang
- Yuekun Zhu
- Daxun Piao
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Affiliations: Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: February 27, 2019 https://doi.org/10.3892/ijo.2019.4733
Pages: 1691-1703
Copyright: © Xing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite considerable recent advancements in colorectal cancer (CRC) therapy, the prognosis of patients with advanced disease remains poor. Further understanding of the molecular mechanisms and treatment strategies of this disease is required. Zinc finger protein 692 (ZNF692), also known as AREBP and Zfp692, was first reported to have an important role in gluconeogenesis. A recent study demonstrated that ZNF692 is overexpressed in lung adenocarcinoma (LUAD) tissues and that ZNF692 knockdown inhibited LUAD cell proliferation, migration, and invasion both in vitro and in vivo. However, the role of ZNF692 in colon adenocarcinoma (COAD) remains unclear. The present study revealed that ZNF692 was upregulated in COAD tissues and cells and that high ZNF692 expression was significantly correlated with lymph node metastasis, distant metastasis and tumor stage in COAD patients. Gain‑ and loss‑of‑function experiments were employed to identify the function of ZNF692 in COAD progression. In vitro and in vivo assays revealed that ZNF692 promoted COAD cell proliferation, migration and invasion. Furthermore, western blot analysis demonstrated that the effects of ZNF692 were mediated by upregulating cyclin D1, cyclin‑dependent kinase 2 (CDK2) and matrix metalloproteinase‑9 (MMP‑9) and by downregulating p27Kip1 through the phosphoinositide 3‑kinase/AKT signaling pathway. Collectively, these data indicated that ZNF692 may serve as a novel oncogene and a potential treatment target in COAD patients.

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