Prediction and identification of transcriptional regulatory elements at the lung cancer‑specific DKK1 locus

Gao,Yan; Du,Xian; Zeng,Jing; Wu,Ruimin; Chen,Yijia; Li,Fuyan; Li,Wei; Zhou,Hong; Yang,Yi; Pei,Zhijun

doi:10.3892/ol.2018.8638

Prediction and identification of transcriptional regulatory elements at the lung cancer‑specific DKK1 locus

Authors:
- Yan Gao
- Xian Du
- Jing Zeng
- Ruimin Wu
- Yijia Chen
- Fuyan Li
- Wei Li
- Hong Zhou
- Yi Yang
- Zhijun Pei
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Affiliations: Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of General Surgery II, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: May 4, 2018 https://doi.org/10.3892/ol.2018.8638
Pages: 137-144
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The glycoprotein dickkopf 1 (DKK1) is highly expressed in lung cancer cell lines and tissues. Our previous study demonstrated that DKK1 promoter activity is low in lung cancer cell lines. This may be because it lacks the necessary transcriptional regulatory elements (TREs) required for higher activity levels. However, it is difficult to computationally predict functionally significant TREs, as TREs from different locations can affect large segments of distant DNA. The Encyclopedia of DNA Elements project features multiple integrated technologies and approaches for the discovery and definition of functional elements, including enhancer elements and enhancer‑blocking insulators. In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis‑acting enhancer elements were identified by a dual‑luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis‑acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy.

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