LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells
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Elsa M. Reyes-Reyes1, Ivan Aispuro1, Marco A. Tavera-Garcia1, Matthew Field1, Sara Moore1, Irma Ramos1,3 and Kenneth S. Ramos1,2,3
1University of Arizona College of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Tucson, AZ, USA
2University of Arizona Cancer Center, Tucson, AZ, USA
3Center for Applied Genetics and Genomic Medicine, University of Arizona Health Sciences, Tucson, AZ, USA
Kenneth S. Ramos, email: [email protected]
Keywords: LINE-1, EMT programming, oncogenesis
Received: August 23, 2017 Accepted: October 10, 2017 Published: October 23, 2017
Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFβ1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.
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