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http://dx.doi.org/10.5483/BMBRep.2018.51.1.163

Dual effects of a CpG-DNAzyme targeting mutant EGFR transcripts in lung cancer cells: TLR9 activation and EGFR downregulation  

Jang, Dahye (Department of Bioscience and Biotechnology, Konkuk University)
Baek, Yu Mi (Department of Bioscience and Biotechnology, Konkuk University)
Park, Hanna (Department of Bioscience and Biotechnology, Konkuk University)
Hwang, Yeo Eun (Department of Bioscience and Biotechnology, Konkuk University)
Kim, Dong-Eun (Department of Bioscience and Biotechnology, Konkuk University)
Publication Information
BMB Reports / v.51, no.1, 2018 , pp. 27-32 More about this Journal
Abstract
Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells.
Keywords
CpG site; DNAzyme; EGFR mutation; Lung cancer; Toll-like receptor 9;
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Times Cited By KSCI : 1  (Citation Analysis)
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