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

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.

An Immune-Related Signature Predicts Survival in Patients With Lung Adenocarcinoma

“…From this, a prognostic prediction model was constructed, the RiskScore of patients was calculated, and prediction and verification were also carried out. Among all 14 prognosis-specific immunerelated genes, 9 (e.g., PSMD11, PPIA, MIF, BMP5, DKK1, PDGFB, ANGPTL4, IL1R2, and THRB) (26)(27)(28)(29)(30)(31)(32)(33)(34) have been reported to be involved in the immune microenvironmentassociated pathogenesis of lung adenocarcinoma or suggested to be significant predictors of recurrence-free or overall survival. This implies that our bioinformatics analysis using TCGA and ImmPort cohorts has prognostic value.…”

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

“…By predicting and identifying the transcriptional regulatory elements of lung cancer-specific DKK1 locus, they confirmed that specific transcriptional regulatory elements can promote DKK1 promoter activity and lead to high expression of DKK1. 23 Through bioinformatics analysis of four pancreatic cancer transcriptome microarray data sets, they confirmed that DKK1 is highly expressed in pancreatic cancer. 24 Taken together, these studies confirmed that DKK1 expression in cancer is diverse.…”